Increased matrix stiffness of nucleus pulposus(NP)tissue is a main feature of intervertebral disc degeneration(IVDD)and affects various functions of nucleus pulposus cells(NPCs).Glycolysis is the main energy source fo...Increased matrix stiffness of nucleus pulposus(NP)tissue is a main feature of intervertebral disc degeneration(IVDD)and affects various functions of nucleus pulposus cells(NPCs).Glycolysis is the main energy source for NPC survival,but the effects and underlying mechanisms of increased extracellular matrix(ECM)stiffness on NPC glycolysis remain unknown.In this study,hydrogels with different stiffness were established to mimic the mechanical environment of NPCs.Notably,increased matrix stiffness in degenerated NP tissues from IVDD patients was accompanied with impaired glycolysis,and NPCs cultured on rigid substrates exhibited a reduction in glycolysis.展开更多
Cells are exposed to various mechanical forces,including extracellular and intracellular forces such as stiffness,tension,compression,viscosity,and shear stress,which regulate cell biology.The process of transducing m...Cells are exposed to various mechanical forces,including extracellular and intracellular forces such as stiffness,tension,compression,viscosity,and shear stress,which regulate cell biology.The process of transducing mechanical stimuli into biochemical signals is termed mechanotransduction.These mechanical forces can regulate protein and gene expression,thereby impacting cell morphology,adhesion,proliferation,apoptosis,and migration.During cancer development,significant changes in extracellular and intracellular mechanical properties occur,resulting in altered mechanical inputs to which cells are exposed.MicroRNAs(miRNAs),key post-transcriptional regulators of gene and protein expression,are increasingly recognized as mechanosensitive molecules involved in cancer development.In this review,we summarize the primary cellular pathways involved in force sensing and mechanotransduction,emphasizing the role of forces in miRNA biogenesis and expression,as well as their influence on the regulation of key mechanotransducers.Furthermore,we focus on recent evidence regarding the induction or repression of miRNAs involved in cancer development by mechanical forces and their impact on the regulation of proteins that contribute to cancer progression.展开更多
The interaction between the lactate receptor GPR81(also known as hydroxycarboxylic acid receptor 1,or HCAR1)and Splicing Factor Proline-and Glutamine-Rich protein promotes the tumor cell malignancy.GPR81 nuclear trans...The interaction between the lactate receptor GPR81(also known as hydroxycarboxylic acid receptor 1,or HCAR1)and Splicing Factor Proline-and Glutamine-Rich protein promotes the tumor cell malignancy.GPR81 nuclear translocation plays an important role in driving cancer progression and could serve as a potential therapeutic target.Yang et al concluded in their study that lactate and its receptor,GPR81,play crucial roles in cancer progression,and are key players in linking the lactate-rich tumor microenvironment to cancer cell behavior.The ability of nuclear GPR81 to directly regulate gene expression,combined with extracellular matrix-mediated mechanical signaling,creates a potentially robust system for the coordinated adaptation and survival of cancer cells.Understanding these interactions could lead to the discovery of new therapeutic targets and improved treatment strategies for cancer.展开更多
Piezo2,a mechanosensitive ion channel,serves as a crucial mechanotransducer in dental primary afferent(DPA)neurons and is potentially involved in hypersensitivity to mild mechanical irritations observed in dental pati...Piezo2,a mechanosensitive ion channel,serves as a crucial mechanotransducer in dental primary afferent(DPA)neurons and is potentially involved in hypersensitivity to mild mechanical irritations observed in dental patients.Given Piezo2’s widespread expression across diverse subpopulations of DPA neurons,this study aimed to characterize the mechanosensory properties of Piezo2-expressing DPA neurons with a focus on distinct features of voltage-gated sodium channels(VGSCs)and neuropeptide profiles.Using whole-cell patch-clamp recordings,we observed mechanically activated action potentials(APs)and classified AP waveforms based on the presence or absence of a hump during the repolarization phase.Single-cell reverse transcription polymerase chain reaction combined with patch-clamp recordings revealed specific associations between AP waveforms and molecular properties,including tetrodotoxin-resistant VGSCs(NaV1.8 and NaV1.9)and TRPV1 expression.Reanalysis of the transcriptomic dataset of DPA neurons identified correlations between neuropeptides—including two CGRP isoforms(α-CGRP andβ-CGRP),Substance P,and Galanin—and the expression of NaV1.8 and NaV1.9,which were linked to defined AP subtypes.These molecular associations were further validated in Piezo2+DPA neurons using fluorescence in situ hybridization.Together,these findings highlight the electrophysiological and neurochemical heterogeneity of Piezo2-expressing DPA neurons and their specialized roles in distinct mechanosensory signal transmission.展开更多
OBJECTIVE:To investigate whether electroacupuncture(EA)therapy for overactive bladder(OAB)exerts its effect by modulating mechanosensitive channels in the urothelium,thereby improving bladder sensory function.METHODS:...OBJECTIVE:To investigate whether electroacupuncture(EA)therapy for overactive bladder(OAB)exerts its effect by modulating mechanosensitive channels in the urothelium,thereby improving bladder sensory function.METHODS:In this study,a rat model of OAB was created by using intraperitoneal injections of cyclophosphamide.We performed either EA or bladder perfusion with HC-067047[a transient receptor potential vanilloid 4(TRPV4)antagonist]and assessed the efficacy of electroacupuncture in the treatment of OAB in rats via urodynamic determination and Void spot assay.tissue morphology,distribution and expression of the TRPV4protein and the amount of adenosine triphosphate(ATP)and Ca2+released from urothelial cells in each group of rats were observed to identify the mechanism by which electroacupuncture improves OAB in rats.RESULTS:EA ameliorated bladder function and voiding behaviour,improved bladder uroepithelial tissue morphology,and significantly reduced the immunofluorescence intensity and the mRNA and protein expression levels of TRPV4 in the uroepithelium of OAB rats.Moreover,the simulated mechanical stimulationinduced increases in Ca^(2+)concentration and the release of ATP and acetylcholine(Ach)from bladder urothelial cells were inhibited.The changes in EA followed the same trend as those in HC-067047.CONCLUSIONS:These results suggest that EA inhibits bladder sensory function by downregulating the expression of mechanically activated TRPV4 ion channels distributed in bladder urothelial cells,which correspondingly decreases the inward flow of extracellular Ca^(2+)and reduces the release of ATP and Ach,thereby attenuating excitatory signals.展开更多
Cells within tissues are subject to various mechanical forces,including hydrostatic pressure,shear stress,compression,and tension.These mechanical stimuli can be converted into biochemical signals through mechanorecep...Cells within tissues are subject to various mechanical forces,including hydrostatic pressure,shear stress,compression,and tension.These mechanical stimuli can be converted into biochemical signals through mechanoreceptors or cytoskeleton-dependent response processes,shaping the microenvironment and maintaining cellular physiological balance.Several studies have demonstrated the roles of Yes-associated protein(YAP)and its homolog transcriptional coactivator with PDZ-binding motif(TAZ)as mechanotransducers,exerting dynamic influence on cellular phenotypes including differentiation and disease pathogenesis.This regulatory function entails the involvement of the cytoskeleton,nucleoskeleton,integrin,focal adhesions(FAs),and the integration of multiple signaling pathways,including extracellular signal-regulated kinase(ERK),wingless/integrated(WNT),and Hippo signaling.Furthermore,emerging evidence substantiates the implication of long non-coding RNAs(lncRNAs)as mechanosensitive molecules in cellular mechanotransduction.In this review,we discuss the mechanisms through which YAP/TAZ and lncRNAs serve as effectors in responding to mechanical stimuli.Additionally,we summarize and elaborate on the crucial signal molecules involved in mechanotransduction.展开更多
In order to quantify the poroelastic mechanical signals conduction and evaluate the biomechanical effectiveness of functional units(osteocyte processes,canaliculi and lacuna)in lacunar-canalicular system(LCS),a multis...In order to quantify the poroelastic mechanical signals conduction and evaluate the biomechanical effectiveness of functional units(osteocyte processes,canaliculi and lacuna)in lacunar-canalicular system(LCS),a multiscale poroelastic finite element model was established by using the Comsol Multiphysics software.The poroelastic mechanical signals(pore pressure,fluid velocity,von-Mises stress,strain)were analyzed inside the osteon-osteocyte system.The effects of osteocyte(OCY)’s shape(ellipse and circle),long axis directions(horizontal and vertical)and mechanical properties(Elastic modulus and permeability)on its poroelastic responses were examined.It is found that the OCY processes is the best mechanosensor compared with the OCY body,lacunae and canaliculi.The mechanotransduction ability of the elliptic shaped OCY is stronger than that of circular shaped.The pore pressure and flow velocity around OCYs increase as the elastic modulus and permeability of OCY increase.The established model can be used for studying the mechanism of bone mechanotransduction at the multiscale level.展开更多
Tendon is a mechanosensitive tissue that transmits force from muscle to bone.Physiological loading contributes to maintaining the homeostasis and adaptation of tendon,but aberrant loading may lead to injury or failed ...Tendon is a mechanosensitive tissue that transmits force from muscle to bone.Physiological loading contributes to maintaining the homeostasis and adaptation of tendon,but aberrant loading may lead to injury or failed repair.It is shown that stem cells respond to mechanical loading and play an essential role in both acute and chronic injuries,as well as in tendon repair.In the process of mechanotransduction,mechanical loading is detected by mechanosensors that regulate cell differentiation and proliferation via several signaling pathways.In order to better understand the stem-cell response to mechanical stimulation and the potential mechanism of the tendon repair process,in this review,we summarize the source and role of endogenous and exogenous stem cells active in tendon repair,describe the mechanical response of stem cells,and finally,highlight the mechanotransduction process and underlying signaling pathways.展开更多
Mechanotransduction,a conversion of mechanical forces into biochemical signals,is essential for human development and physiology.It is observable at all levels ranging from the whole body,organs,tissues,organelles dow...Mechanotransduction,a conversion of mechanical forces into biochemical signals,is essential for human development and physiology.It is observable at all levels ranging from the whole body,organs,tissues,organelles down to molecules.Dysregulation results in various diseases such as muscular dystrophies,hypertension-induced vascular and cardiac hypertrophy,altered bone repair and cell deaths.Since mechanotransduction occurs at nanoscale,nanosciences and applied nanotechnology are powerful for studying molecular mechanisms and pathways of mechanotransduction.Atomic force microscopy,magnetic and optical tweezers are commonly used for force measurement and manipulation at the single molecular level.Force is also used to control cells,topographically and mechanically by specific types of nano materials for tissue engineering.Mechanotransduction research will become increasingly important as a sub-discipline under nanomedicine.Here we review nanotechnology approaches using force measurements and manipulations at the molecular and cellular levels during mechanotransduction,which has been increasingly play important role in the advancement of nanomedicine.展开更多
Gravity plays a central role in vertebrate development and evolution.Mechanotransduction involves the tensile tethering of veins and arteries,connections between the epidermis and dermis in skin,tensile stress concent...Gravity plays a central role in vertebrate development and evolution.Mechanotransduction involves the tensile tethering of veins and arteries,connections between the epidermis and dermis in skin,tensile stress concentrations that occur at tissue interfaces,cell-cell interactions,cell-collagen fiber stress transfer in extracellular matrix and fluid shear flow.While attention in the past has been directed at understanding the myriad of biochemical players associated with mechanotransduction pathways,less attention has been focused on determining the tensile mechanical behavior of tissues in vivo.Fibroblasts sit on the surface of collagen fibers in living skin and exert a retractile force on the fibers.This retractile force pulls against the tension in collagen fibers in skin.After fibroblast-collagen fiber interactions are altered either by changes in fibroblast adhesion or after formation of cancer associated fibroblasts,and changes in cell junctions,alterations in the retractive force leads to changes in mechanotransduction.The purpose of this paper is to present a model of tensile forces that occur at the fibroblast-collagen fiber interface and how these forces are important in extracellular matrix physiology in health and disease.展开更多
It is known that mechanical forces play critical roles in physiology and diseases but the underlying mechanisms remain largely unknown[1].Most studies on the role of forces focus on cell surface molecules and cytoplas...It is known that mechanical forces play critical roles in physiology and diseases but the underlying mechanisms remain largely unknown[1].Most studies on the role of forces focus on cell surface molecules and cytoplasmic proteins.However,increasing evidence suggests that nuclear mechanotransduction impacts nuclear activities and functions.Recently we have revealed that transgene dihydrofolate reductase(DHFR)gene expression is directly upregulated via cell surface forceinduced stretching of chromatin [2].Here we show that endogenous genes are also upregulated directly by force via integrins.We present evidence on an underlying mechanism of how gene transcription is regulated by force.We have developed a technique of elastic round microgels to quantify 3D tractions in vitro and in vivo[3].We report a synthetic small molecule(which has been stiffened structurally)that inhibits malignant tumor repopulating cell growth in a low-stiffness(force)microenvironment and cancer metastasis in mouse models without detectable toxicity[4].These findings suggest that direct nuclear mechanotransduction impacts mechanobiology and mechanomedicine at cellular and molecular levels.展开更多
Cells in vivo reside within a complex microenvironment that is rich in biological,chemical and mechanical cues,playing critical roles in regulating cellular activities(e.g.,proliferation,migration,differentiation)both...Cells in vivo reside within a complex microenvironment that is rich in biological,chemical and mechanical cues,playing critical roles in regulating cellular activities(e.g.,proliferation,migration,differentiation)both spatially and temporally.Although it is well accepted that biochemical cues can significantly influence cell functions,accumulating evidence has also shown that mechanical feedback from the cell microenvironment(e.g.,stiffness of ECM,morphology,and tension force)also plays an important role in controlling cell fate.Disequilibrium of the mechanical microenvironment is associated with a series of diseases,such as cancer migration and tissue fibrosis.Thus,there is a pressing need to understand how cells transduce these mechanobiological cues.The cell cytoskeleton is linked to both the nuclear lamina via LINC complexes and to focal adhesions.This enables the intriguing possibility that forces directly transduced by the nucleus might in fact affect gene expression.Can force transmitted to nucleus and associated alterations to the special organization of genome inside the nucleus modulate gene expression programmes and change cell behaviors? This kind of putative mechanotransduction dominated by the nucleus is termed as nuclear mechanotransduction.Evidence shows that isolated nuclei regulate their stiffness to in response to force applied on nesprin with integrated nuclear lamina and emerin required.Another example is that the force applied on integrins in focal adhesions can be transmitted through actin filaments to the LINC complex and then stretch the chromatin directly through lamina-chromatin interactions.However,the mechanism of nuclear mechanotransduction is still unclear.Three hypotheses have been proposed.The first proposed mechanism is that the proteins on the nuclear lamina are phosphorylated induced by force and their special organization is changed to regulate downstream signal transduction.Transcription factors like YAP and calcium ions would enter the nucleus in the context of force stretching the nuclear lamina and opening nuclear pore complexes(NPC)and calcium channels.Another proposed hypothesis in this case is that force propagated through the cytoskeleton stretches,opens or condenses chromatin directly,leading to an entirely different genome organization.Nevertheless,due to the lack of research methods and instruments,researchers have not reached a consensus on how cells sense external forces and react specifically through nucleus.In this study,we used micropatterned techniques to modify poly(N-isopropyl-acrylamide)(PA)hydrogel surface with fibronectin(FN)which promote cell adhesion to shape-engineer the cells to investigate the effects of matrix stiffness on nuclear mechanotransduction.To illustrate the impact on nuclear shape induced by matrix stiffness,the nuclei were stained byDAPI and observed by a laser confocal microscopy with small step sizes.The nuclear shape index(NSI),which indicate the variation of projected nuclear shape was firstly researched thoroughly.Meanwhile,the nuclear height,width and volume were characterized in this study.To investigate the force transmitted to the nuclei in cells cultured on hydrogels with multiple stiffness,the cell traction force was measured and the cytoskeleton like actin cap was studied by pharmacological treatments.We also found that the impacts of matrix stiffness on nuclear mechanics,which indicated by the condensation of chromatin and the overexpression of Lamin A/C.展开更多
Introduction Mechanotransduction has demonstrated potentials for tissue adaptation in vivo and in vitro. It is well documented that ultrasound,as a mechanical signal,can produce a wide variety of biological effects in...Introduction Mechanotransduction has demonstrated potentials for tissue adaptation in vivo and in vitro. It is well documented that ultrasound,as a mechanical signal,can produce a wide variety of biological effects in vitro and in vivo [1]. As an example,展开更多
Mesenchymal stem cells(MSCs)and their byproducts have been widely validated as potential therapeutic products for regenerative medicine.The therapeutic effects result mainly from the paracrine activity of MSCs,which c...Mesenchymal stem cells(MSCs)and their byproducts have been widely validated as potential therapeutic products for regenerative medicine.The therapeutic effects result mainly from the paracrine activity of MSCs,which consists of the secretion of bioactive molecules,whether dispersed in medium conditioned by cell culture or encapsulated in extracellular vesicles.The composition of the MSC secretome,which represents the set of these secreted cellular products,is crucial for the performance of the desired therapeutic functions.Different cell culture strategies have been employed to adjust the secretome composition of MSCs to obtain the best therapeutic responses for different clinical contexts.However,the manipulation of culture conditions has focused mainly on the use of different biochemical elements for the preconditioning of MSCs and less on the physical conditions of the cell culture environment.Herein,we offer our point of view regarding the importance of the physical properties of cell culture substrates and their mechanotransduction responses in preconditioning the MSCs secretome.We highlight the relevance of studying mechanotransduction events associating cell morphology and the modulation of gene expression to customize and expand the use of MSCs secretomes.展开更多
Polycystins are key mechanosensor proteins able to respond to mechanical forces of external or internal origin. They are widely expressed in primary cilium and plasma membrane of several cell types including kidney, v...Polycystins are key mechanosensor proteins able to respond to mechanical forces of external or internal origin. They are widely expressed in primary cilium and plasma membrane of several cell types including kidney, vascular endothelial and smooth muscle cells,osteoblasts and cardiac myocytes modulating their physiology. Interaction of polycystins with diverse ion channels, cell-cell and cell-extracellular matrix junctional proteins implicates them in the regulation of cell structure, mechanical force transmission and mechanotransduction. Their intracellular localization in endoplasmic reticulum further regulates subcellular trafficking and calcium homeostasis, finely-tuning overall cellular mechanosensitivity. Aberrant expression or genetic alterations of polycystins lead to severe structural and mechanosensing abnormalities including cyst formation, deregulated flow sensing, aneurysms,defective bone development and cancer progression,highlighting their vital role in human physiology.展开更多
Mechanotransduction has been proven to be one of the most significant variables in bone remodeling and its alterations have been shown to result in a variety of bone diseases. Osteoporosis, Paget's disease, orthop...Mechanotransduction has been proven to be one of the most significant variables in bone remodeling and its alterations have been shown to result in a variety of bone diseases. Osteoporosis, Paget's disease, orthopedic disorders, osteopetrosis as well as hyperparathyroidism and hyperthyroidism all comprise conditions which have been linked with deregulated bone remodeling. Although the significance of mechanotransduction for bone health and disease is unquestionable, the mechanisms behind this important process have not been fully understood. This review will discuss the molecules that have been found to be implicated in mechanotransduction, as well as the mechanisms underlying bone health and disease, emphasizing on what is already known as well as new molecules potentially taking part in conveying mechanical signals from the cell surface towards the nucleus under physiological or pathologic conditions. It will also focus on the model systems currently used in mechanotransduction studies, like osteoblast-like cells as well as three-dimensional constructs and their applications among others. It will also examine the role of mechanostimulatory techniques in preventing and treating bone degenerative diseases and consider theirapplications in osteoporosis, craniofacial development, skeletal deregulations, fracture treatment, neurologic injuries following stroke or spinal cord injury, dentistry, hearing problems and bone implant integration in the near future.展开更多
BACKGROUND The development of cancer is thought to involve the dynamic crosstalk between the tumor cells and the microenvironment they inhabit.Such crosstalk is thought to involve mechanotransduction,a process whereby...BACKGROUND The development of cancer is thought to involve the dynamic crosstalk between the tumor cells and the microenvironment they inhabit.Such crosstalk is thought to involve mechanotransduction,a process whereby the cells sense mechanical cues such as stiffness,and translate these into biochemical signals,which have an impact on the subsequent cellular activities.Bibliometric analysis is a statistical method that involves investigating different aspects(including authors’names and affiliations,article keywords,journals and citations)of large volumes of literature.Despite an increase in mechanotransduction-related research in recent years,there are currently no bibliometric studies that describe the global status and trends of mechanotransduction-related research in the cancer field.AIM To investigate the global research status and trends of mechanotransduction in cancer from a bibliometric viewpoint.METHODS Literature on mechanotransduction in cancer published from January 1,1900 to December 31,2022 was retrieved from the Web of Science Core Collection.Excel and GraphPad software carried out the statistical analysis of the relevant author,journal,organization,and country information.The co-authorship,keyword cooccurrence,and keyword burst analysis were visualized with VOSviewer and CiteSpace.RESULTS Of 597 publications from 745 institutions in 45 countries were published in 268 journals with 35510 citation times.With 270 articles,the United States is a well-established global leader in this field,and the University of California system,the most productive(n=36)and influential institution(n=4705 citations),is the most highly active in collaborating with other organizations.Cancers was the most frequent publisher with the highest H-index.The most productive researcher was Valerie M.Weaver,with 10 publications.The combined analysis of concurrent and burst keywords revealed that the future research hotspots of mechanotransduction in cancer were related to the plasma membrane,autophagy,piezo1/2,heterogeneity,cancer diagnosis,and post-transcriptional modifications.CONCLUSION Mechanotransduction-related cancer research remains a hot topic.The United States is in the leading position of global research on mechano-oncology after almost 30 years of investigations.Research group cooperations exist but remain largely domestic,lacking cross-national communications.The next big topic in this field is to explore how the plasma membrane and its localized mechanosensor can transduce mechanical force through post-transcriptional modifications and thereby participate in cellular activity regulations and cancer development.展开更多
Microspheres(MPs)and porous microspheres(PMPs)are the two most widely used microparticles in tissue engineering and stem cell therapy.However,how stem cells perceive the topological differences between them to regulat...Microspheres(MPs)and porous microspheres(PMPs)are the two most widely used microparticles in tissue engineering and stem cell therapy.However,how stem cells perceive the topological differences between them to regulate cell function remains to be unclear.Here,we systematically studied the changes in stem cell function under the action of MPs and PMPs and elucidated the related mechanisms.Our findings show that the porous structure of PMPs can be sensed by focal adhesions(FAs),which triggers the synthesis of F-actin to inhibit the phosphorylation and degradation of Yes-associated protein(YAP),while also transmitting stress to the nucleus through the contraction of F-actin,thereby enhancing the nuclear translocation of YAP protein.The activation of YAP significantly enhances the proliferation,osteogenesis,paracrine and glucose metabolism of BMSCs,making them exhibit stronger bone repair ability in both in vivo and in vitro experiments.In summary,this study provides a comprehensive and reliable understanding of the behavior of BMSCs in response to MPs and PMPs.It also deepens our understanding of the association between microparticles’topological cues and biological functions,which will provide valuable guidance for the construction of bone tissue engineering(BTE)scaffolds.展开更多
Mechanotransduction is the process that enables the conversion of mechanical cues into biochemical signaling.While all our cells are well known to be sensitive to such stimuli,the details of the systemic interaction b...Mechanotransduction is the process that enables the conversion of mechanical cues into biochemical signaling.While all our cells are well known to be sensitive to such stimuli,the details of the systemic interaction between mechanical input and inflammation are not well integrated.Often,indeed,they are considered and studied in relatively compartmentalized areas,and we therefore argue here that to understand the relationship of mechanical stimuli with inflammation-with a high translational potential-it is crucial to offer and analyze a unified view of mechanotransduction.We therefore present here pathway representation,recollected with the standard systems biology markup language(SBML)and explored with network biology approaches,offering RAC1 as an exemplar and emerging molecule with potential for medical translation.展开更多
Group 2 innate lymphoid cells(ILC2s)are central effectors of type 2 immune responses in the lung;however,how mechanical cues regulate their function remains unclear.Here,we identified the mechanosensitive ion channel ...Group 2 innate lymphoid cells(ILC2s)are central effectors of type 2 immune responses in the lung;however,how mechanical cues regulate their function remains unclear.Here,we identified the mechanosensitive ion channel Piezo1 as a key regulator of ILC2 effector function through translational control.Piezo1 is highly expressed in murine and human ILC2s,and its activation by mechanical stress or the Piezo1 agonist,Yoda1 induces calcium influx,triggering mTOR signaling and selectively enhancing IL-13 protein production.Conditional deletion of Piezo1 in ILC2s reduced mTOR activation and puromycin incorporation,leading to impaired protein synthesis and attenuated lung inflammation and fibrosis in the IL-33,Alternaria alternata,and bleomycin models.scRNA-seq and scATAC-seq confirmed that Piezo1-deficient ILC2s retained Il13 transcription and chromatin accessibility but presented translational suppression,as evidenced by protein‒mRNA interactions.Pharmacologic mTOR inhibition phenocopied Piezo1 loss,supporting the functional relevance of the Piezo1–mTOR axis.These findings demonstrate that Piezo1 functions as a mechanosensor that integrates biomechanical cues to regulate cytokine output via mTOR-mediated translation.Targeting Piezo1 signaling or its downstream effectors may provide therapeutic benefits in type 2 inflammation–associated lung diseases.展开更多
基金supported by the National Nature Science Foundation of China(No.82002345 to J.D and 81902179 to L.S)the Gusu Talent Program(No.Qngg2022008 and GSWS2021027 to J.D)the Preliminary Research Project of the Second Affiliated Hospital of Soochow University(No.SDFEYBS1905 to J.D).
文摘Increased matrix stiffness of nucleus pulposus(NP)tissue is a main feature of intervertebral disc degeneration(IVDD)and affects various functions of nucleus pulposus cells(NPCs).Glycolysis is the main energy source for NPC survival,but the effects and underlying mechanisms of increased extracellular matrix(ECM)stiffness on NPC glycolysis remain unknown.In this study,hydrogels with different stiffness were established to mimic the mechanical environment of NPCs.Notably,increased matrix stiffness in degenerated NP tissues from IVDD patients was accompanied with impaired glycolysis,and NPCs cultured on rigid substrates exhibited a reduction in glycolysis.
文摘Cells are exposed to various mechanical forces,including extracellular and intracellular forces such as stiffness,tension,compression,viscosity,and shear stress,which regulate cell biology.The process of transducing mechanical stimuli into biochemical signals is termed mechanotransduction.These mechanical forces can regulate protein and gene expression,thereby impacting cell morphology,adhesion,proliferation,apoptosis,and migration.During cancer development,significant changes in extracellular and intracellular mechanical properties occur,resulting in altered mechanical inputs to which cells are exposed.MicroRNAs(miRNAs),key post-transcriptional regulators of gene and protein expression,are increasingly recognized as mechanosensitive molecules involved in cancer development.In this review,we summarize the primary cellular pathways involved in force sensing and mechanotransduction,emphasizing the role of forces in miRNA biogenesis and expression,as well as their influence on the regulation of key mechanotransducers.Furthermore,we focus on recent evidence regarding the induction or repression of miRNAs involved in cancer development by mechanical forces and their impact on the regulation of proteins that contribute to cancer progression.
文摘The interaction between the lactate receptor GPR81(also known as hydroxycarboxylic acid receptor 1,or HCAR1)and Splicing Factor Proline-and Glutamine-Rich protein promotes the tumor cell malignancy.GPR81 nuclear translocation plays an important role in driving cancer progression and could serve as a potential therapeutic target.Yang et al concluded in their study that lactate and its receptor,GPR81,play crucial roles in cancer progression,and are key players in linking the lactate-rich tumor microenvironment to cancer cell behavior.The ability of nuclear GPR81 to directly regulate gene expression,combined with extracellular matrix-mediated mechanical signaling,creates a potentially robust system for the coordinated adaptation and survival of cancer cells.Understanding these interactions could lead to the discovery of new therapeutic targets and improved treatment strategies for cancer.
基金supported by the National Research Foundation(NRF)of Korea(grant number:RS-2022-NR072217 to P.RL,RS-2021-NR059709,RS-2023-00264409,and RS-2024-00441103)funded by the Korean government(MSIT).
文摘Piezo2,a mechanosensitive ion channel,serves as a crucial mechanotransducer in dental primary afferent(DPA)neurons and is potentially involved in hypersensitivity to mild mechanical irritations observed in dental patients.Given Piezo2’s widespread expression across diverse subpopulations of DPA neurons,this study aimed to characterize the mechanosensory properties of Piezo2-expressing DPA neurons with a focus on distinct features of voltage-gated sodium channels(VGSCs)and neuropeptide profiles.Using whole-cell patch-clamp recordings,we observed mechanically activated action potentials(APs)and classified AP waveforms based on the presence or absence of a hump during the repolarization phase.Single-cell reverse transcription polymerase chain reaction combined with patch-clamp recordings revealed specific associations between AP waveforms and molecular properties,including tetrodotoxin-resistant VGSCs(NaV1.8 and NaV1.9)and TRPV1 expression.Reanalysis of the transcriptomic dataset of DPA neurons identified correlations between neuropeptides—including two CGRP isoforms(α-CGRP andβ-CGRP),Substance P,and Galanin—and the expression of NaV1.8 and NaV1.9,which were linked to defined AP subtypes.These molecular associations were further validated in Piezo2+DPA neurons using fluorescence in situ hybridization.Together,these findings highlight the electrophysiological and neurochemical heterogeneity of Piezo2-expressing DPA neurons and their specialized roles in distinct mechanosensory signal transmission.
基金Natural Science Foundation-funded Project:Research on the Effect of Acupuncture in Regulating Bladder Excitability based on the Generation and Transmission of Afferent Information from Urinary Control(No.82174516)Investigation into the Mechanism of Acupuncture-regulated Bladder Excitability based on Sensory Nerve Mechanotransduction Signaling(No.82474645)。
文摘OBJECTIVE:To investigate whether electroacupuncture(EA)therapy for overactive bladder(OAB)exerts its effect by modulating mechanosensitive channels in the urothelium,thereby improving bladder sensory function.METHODS:In this study,a rat model of OAB was created by using intraperitoneal injections of cyclophosphamide.We performed either EA or bladder perfusion with HC-067047[a transient receptor potential vanilloid 4(TRPV4)antagonist]and assessed the efficacy of electroacupuncture in the treatment of OAB in rats via urodynamic determination and Void spot assay.tissue morphology,distribution and expression of the TRPV4protein and the amount of adenosine triphosphate(ATP)and Ca2+released from urothelial cells in each group of rats were observed to identify the mechanism by which electroacupuncture improves OAB in rats.RESULTS:EA ameliorated bladder function and voiding behaviour,improved bladder uroepithelial tissue morphology,and significantly reduced the immunofluorescence intensity and the mRNA and protein expression levels of TRPV4 in the uroepithelium of OAB rats.Moreover,the simulated mechanical stimulationinduced increases in Ca^(2+)concentration and the release of ATP and acetylcholine(Ach)from bladder urothelial cells were inhibited.The changes in EA followed the same trend as those in HC-067047.CONCLUSIONS:These results suggest that EA inhibits bladder sensory function by downregulating the expression of mechanically activated TRPV4 ion channels distributed in bladder urothelial cells,which correspondingly decreases the inward flow of extracellular Ca^(2+)and reduces the release of ATP and Ach,thereby attenuating excitatory signals.
基金supported by the National Natural Science Foundation for Distinguished Young Scholars of China(No.32225014)the“Lingyan”R&D Research and Development Project(No.2023C03023)+2 种基金the National Key R&D Program of China(No.2021YFC2700903)the National Natural Science Foundation of China(Nos.81672791 and 81872300)the Zhejiang Provincial Natural Science Foundation for Distinguished Young Scholars of China(No.LR18C060002)。
文摘Cells within tissues are subject to various mechanical forces,including hydrostatic pressure,shear stress,compression,and tension.These mechanical stimuli can be converted into biochemical signals through mechanoreceptors or cytoskeleton-dependent response processes,shaping the microenvironment and maintaining cellular physiological balance.Several studies have demonstrated the roles of Yes-associated protein(YAP)and its homolog transcriptional coactivator with PDZ-binding motif(TAZ)as mechanotransducers,exerting dynamic influence on cellular phenotypes including differentiation and disease pathogenesis.This regulatory function entails the involvement of the cytoskeleton,nucleoskeleton,integrin,focal adhesions(FAs),and the integration of multiple signaling pathways,including extracellular signal-regulated kinase(ERK),wingless/integrated(WNT),and Hippo signaling.Furthermore,emerging evidence substantiates the implication of long non-coding RNAs(lncRNAs)as mechanosensitive molecules in cellular mechanotransduction.In this review,we discuss the mechanisms through which YAP/TAZ and lncRNAs serve as effectors in responding to mechanical stimuli.Additionally,we summarize and elaborate on the crucial signal molecules involved in mechanotransduction.
基金supported by the National Natural Science Foundation of China(Grants 11972242,11702183,11632013,and 11572213)the Scientific and Technological Innovation Projects of Colleges and Universities in Shanxi Province(Grant 2017135)Philosophy and Social Sciences Research of Higher Learning Institutions of Shanxi(Grant 2017313).
文摘In order to quantify the poroelastic mechanical signals conduction and evaluate the biomechanical effectiveness of functional units(osteocyte processes,canaliculi and lacuna)in lacunar-canalicular system(LCS),a multiscale poroelastic finite element model was established by using the Comsol Multiphysics software.The poroelastic mechanical signals(pore pressure,fluid velocity,von-Mises stress,strain)were analyzed inside the osteon-osteocyte system.The effects of osteocyte(OCY)’s shape(ellipse and circle),long axis directions(horizontal and vertical)and mechanical properties(Elastic modulus and permeability)on its poroelastic responses were examined.It is found that the OCY processes is the best mechanosensor compared with the OCY body,lacunae and canaliculi.The mechanotransduction ability of the elliptic shaped OCY is stronger than that of circular shaped.The pore pressure and flow velocity around OCYs increase as the elastic modulus and permeability of OCY increase.The established model can be used for studying the mechanism of bone mechanotransduction at the multiscale level.
基金Supported by National Natural Science Foundation of China,No.81871848 and No.81702171and Shenzhen Double Chain Project for Innovation and Development Industry,No.201806081018272960.
文摘Tendon is a mechanosensitive tissue that transmits force from muscle to bone.Physiological loading contributes to maintaining the homeostasis and adaptation of tendon,but aberrant loading may lead to injury or failed repair.It is shown that stem cells respond to mechanical loading and play an essential role in both acute and chronic injuries,as well as in tendon repair.In the process of mechanotransduction,mechanical loading is detected by mechanosensors that regulate cell differentiation and proliferation via several signaling pathways.In order to better understand the stem-cell response to mechanical stimulation and the potential mechanism of the tendon repair process,in this review,we summarize the source and role of endogenous and exogenous stem cells active in tendon repair,describe the mechanical response of stem cells,and finally,highlight the mechanotransduction process and underlying signaling pathways.
基金the National Natural Science Foundation of China(Grant No.31771551 to F.N.).
文摘Mechanotransduction,a conversion of mechanical forces into biochemical signals,is essential for human development and physiology.It is observable at all levels ranging from the whole body,organs,tissues,organelles down to molecules.Dysregulation results in various diseases such as muscular dystrophies,hypertension-induced vascular and cardiac hypertrophy,altered bone repair and cell deaths.Since mechanotransduction occurs at nanoscale,nanosciences and applied nanotechnology are powerful for studying molecular mechanisms and pathways of mechanotransduction.Atomic force microscopy,magnetic and optical tweezers are commonly used for force measurement and manipulation at the single molecular level.Force is also used to control cells,topographically and mechanically by specific types of nano materials for tissue engineering.Mechanotransduction research will become increasingly important as a sub-discipline under nanomedicine.Here we review nanotechnology approaches using force measurements and manipulations at the molecular and cellular levels during mechanotransduction,which has been increasingly play important role in the advancement of nanomedicine.
文摘Gravity plays a central role in vertebrate development and evolution.Mechanotransduction involves the tensile tethering of veins and arteries,connections between the epidermis and dermis in skin,tensile stress concentrations that occur at tissue interfaces,cell-cell interactions,cell-collagen fiber stress transfer in extracellular matrix and fluid shear flow.While attention in the past has been directed at understanding the myriad of biochemical players associated with mechanotransduction pathways,less attention has been focused on determining the tensile mechanical behavior of tissues in vivo.Fibroblasts sit on the surface of collagen fibers in living skin and exert a retractile force on the fibers.This retractile force pulls against the tension in collagen fibers in skin.After fibroblast-collagen fiber interactions are altered either by changes in fibroblast adhesion or after formation of cancer associated fibroblasts,and changes in cell junctions,alterations in the retractive force leads to changes in mechanotransduction.The purpose of this paper is to present a model of tensile forces that occur at the fibroblast-collagen fiber interface and how these forces are important in extracellular matrix physiology in health and disease.
基金supported by funds from National Institutes of Health,USA and Huazhong University of Science and Technology,Wuhan,Chinathe support from Hoeft Professorship at University of Illinois at Urbana-Champaign
文摘It is known that mechanical forces play critical roles in physiology and diseases but the underlying mechanisms remain largely unknown[1].Most studies on the role of forces focus on cell surface molecules and cytoplasmic proteins.However,increasing evidence suggests that nuclear mechanotransduction impacts nuclear activities and functions.Recently we have revealed that transgene dihydrofolate reductase(DHFR)gene expression is directly upregulated via cell surface forceinduced stretching of chromatin [2].Here we show that endogenous genes are also upregulated directly by force via integrins.We present evidence on an underlying mechanism of how gene transcription is regulated by force.We have developed a technique of elastic round microgels to quantify 3D tractions in vitro and in vivo[3].We report a synthetic small molecule(which has been stiffened structurally)that inhibits malignant tumor repopulating cell growth in a low-stiffness(force)microenvironment and cancer metastasis in mouse models without detectable toxicity[4].These findings suggest that direct nuclear mechanotransduction impacts mechanobiology and mechanomedicine at cellular and molecular levels.
基金supported by the National Natural Science Foundation of China ( 11522219,11532009)
文摘Cells in vivo reside within a complex microenvironment that is rich in biological,chemical and mechanical cues,playing critical roles in regulating cellular activities(e.g.,proliferation,migration,differentiation)both spatially and temporally.Although it is well accepted that biochemical cues can significantly influence cell functions,accumulating evidence has also shown that mechanical feedback from the cell microenvironment(e.g.,stiffness of ECM,morphology,and tension force)also plays an important role in controlling cell fate.Disequilibrium of the mechanical microenvironment is associated with a series of diseases,such as cancer migration and tissue fibrosis.Thus,there is a pressing need to understand how cells transduce these mechanobiological cues.The cell cytoskeleton is linked to both the nuclear lamina via LINC complexes and to focal adhesions.This enables the intriguing possibility that forces directly transduced by the nucleus might in fact affect gene expression.Can force transmitted to nucleus and associated alterations to the special organization of genome inside the nucleus modulate gene expression programmes and change cell behaviors? This kind of putative mechanotransduction dominated by the nucleus is termed as nuclear mechanotransduction.Evidence shows that isolated nuclei regulate their stiffness to in response to force applied on nesprin with integrated nuclear lamina and emerin required.Another example is that the force applied on integrins in focal adhesions can be transmitted through actin filaments to the LINC complex and then stretch the chromatin directly through lamina-chromatin interactions.However,the mechanism of nuclear mechanotransduction is still unclear.Three hypotheses have been proposed.The first proposed mechanism is that the proteins on the nuclear lamina are phosphorylated induced by force and their special organization is changed to regulate downstream signal transduction.Transcription factors like YAP and calcium ions would enter the nucleus in the context of force stretching the nuclear lamina and opening nuclear pore complexes(NPC)and calcium channels.Another proposed hypothesis in this case is that force propagated through the cytoskeleton stretches,opens or condenses chromatin directly,leading to an entirely different genome organization.Nevertheless,due to the lack of research methods and instruments,researchers have not reached a consensus on how cells sense external forces and react specifically through nucleus.In this study,we used micropatterned techniques to modify poly(N-isopropyl-acrylamide)(PA)hydrogel surface with fibronectin(FN)which promote cell adhesion to shape-engineer the cells to investigate the effects of matrix stiffness on nuclear mechanotransduction.To illustrate the impact on nuclear shape induced by matrix stiffness,the nuclei were stained byDAPI and observed by a laser confocal microscopy with small step sizes.The nuclear shape index(NSI),which indicate the variation of projected nuclear shape was firstly researched thoroughly.Meanwhile,the nuclear height,width and volume were characterized in this study.To investigate the force transmitted to the nuclei in cells cultured on hydrogels with multiple stiffness,the cell traction force was measured and the cytoskeleton like actin cap was studied by pharmacological treatments.We also found that the impacts of matrix stiffness on nuclear mechanics,which indicated by the condensation of chromatin and the overexpression of Lamin A/C.
基金supported by the NIH (R01 AR52379 & R01 AR49286),U S Army Medical Research and NSBRI
文摘Introduction Mechanotransduction has demonstrated potentials for tissue adaptation in vivo and in vitro. It is well documented that ultrasound,as a mechanical signal,can produce a wide variety of biological effects in vitro and in vivo [1]. As an example,
基金This work was supported by Brazilian National Council for Scientific and Technological Development(CNPq Grant No.442411/2019-7).
文摘Mesenchymal stem cells(MSCs)and their byproducts have been widely validated as potential therapeutic products for regenerative medicine.The therapeutic effects result mainly from the paracrine activity of MSCs,which consists of the secretion of bioactive molecules,whether dispersed in medium conditioned by cell culture or encapsulated in extracellular vesicles.The composition of the MSC secretome,which represents the set of these secreted cellular products,is crucial for the performance of the desired therapeutic functions.Different cell culture strategies have been employed to adjust the secretome composition of MSCs to obtain the best therapeutic responses for different clinical contexts.However,the manipulation of culture conditions has focused mainly on the use of different biochemical elements for the preconditioning of MSCs and less on the physical conditions of the cell culture environment.Herein,we offer our point of view regarding the importance of the physical properties of cell culture substrates and their mechanotransduction responses in preconditioning the MSCs secretome.We highlight the relevance of studying mechanotransduction events associating cell morphology and the modulation of gene expression to customize and expand the use of MSCs secretomes.
文摘Polycystins are key mechanosensor proteins able to respond to mechanical forces of external or internal origin. They are widely expressed in primary cilium and plasma membrane of several cell types including kidney, vascular endothelial and smooth muscle cells,osteoblasts and cardiac myocytes modulating their physiology. Interaction of polycystins with diverse ion channels, cell-cell and cell-extracellular matrix junctional proteins implicates them in the regulation of cell structure, mechanical force transmission and mechanotransduction. Their intracellular localization in endoplasmic reticulum further regulates subcellular trafficking and calcium homeostasis, finely-tuning overall cellular mechanosensitivity. Aberrant expression or genetic alterations of polycystins lead to severe structural and mechanosensing abnormalities including cyst formation, deregulated flow sensing, aneurysms,defective bone development and cancer progression,highlighting their vital role in human physiology.
文摘Mechanotransduction has been proven to be one of the most significant variables in bone remodeling and its alterations have been shown to result in a variety of bone diseases. Osteoporosis, Paget's disease, orthopedic disorders, osteopetrosis as well as hyperparathyroidism and hyperthyroidism all comprise conditions which have been linked with deregulated bone remodeling. Although the significance of mechanotransduction for bone health and disease is unquestionable, the mechanisms behind this important process have not been fully understood. This review will discuss the molecules that have been found to be implicated in mechanotransduction, as well as the mechanisms underlying bone health and disease, emphasizing on what is already known as well as new molecules potentially taking part in conveying mechanical signals from the cell surface towards the nucleus under physiological or pathologic conditions. It will also focus on the model systems currently used in mechanotransduction studies, like osteoblast-like cells as well as three-dimensional constructs and their applications among others. It will also examine the role of mechanostimulatory techniques in preventing and treating bone degenerative diseases and consider theirapplications in osteoporosis, craniofacial development, skeletal deregulations, fracture treatment, neurologic injuries following stroke or spinal cord injury, dentistry, hearing problems and bone implant integration in the near future.
基金Supported by the National Natural Science Foundation of China,No.32200557Natural Science Foundation of Shandong Province,No.ZR2022QH271the Postdoctoral Innovative Projects of Shandong Province,No.SDCX-ZG-202203047.
文摘BACKGROUND The development of cancer is thought to involve the dynamic crosstalk between the tumor cells and the microenvironment they inhabit.Such crosstalk is thought to involve mechanotransduction,a process whereby the cells sense mechanical cues such as stiffness,and translate these into biochemical signals,which have an impact on the subsequent cellular activities.Bibliometric analysis is a statistical method that involves investigating different aspects(including authors’names and affiliations,article keywords,journals and citations)of large volumes of literature.Despite an increase in mechanotransduction-related research in recent years,there are currently no bibliometric studies that describe the global status and trends of mechanotransduction-related research in the cancer field.AIM To investigate the global research status and trends of mechanotransduction in cancer from a bibliometric viewpoint.METHODS Literature on mechanotransduction in cancer published from January 1,1900 to December 31,2022 was retrieved from the Web of Science Core Collection.Excel and GraphPad software carried out the statistical analysis of the relevant author,journal,organization,and country information.The co-authorship,keyword cooccurrence,and keyword burst analysis were visualized with VOSviewer and CiteSpace.RESULTS Of 597 publications from 745 institutions in 45 countries were published in 268 journals with 35510 citation times.With 270 articles,the United States is a well-established global leader in this field,and the University of California system,the most productive(n=36)and influential institution(n=4705 citations),is the most highly active in collaborating with other organizations.Cancers was the most frequent publisher with the highest H-index.The most productive researcher was Valerie M.Weaver,with 10 publications.The combined analysis of concurrent and burst keywords revealed that the future research hotspots of mechanotransduction in cancer were related to the plasma membrane,autophagy,piezo1/2,heterogeneity,cancer diagnosis,and post-transcriptional modifications.CONCLUSION Mechanotransduction-related cancer research remains a hot topic.The United States is in the leading position of global research on mechano-oncology after almost 30 years of investigations.Research group cooperations exist but remain largely domestic,lacking cross-national communications.The next big topic in this field is to explore how the plasma membrane and its localized mechanosensor can transduce mechanical force through post-transcriptional modifications and thereby participate in cellular activity regulations and cancer development.
基金approved by the Ethics Committee of Soochow Uni-versity(Approval No.SUDA20240102A01)and good surgical and therapeutic outcomes were achieved.
文摘Microspheres(MPs)and porous microspheres(PMPs)are the two most widely used microparticles in tissue engineering and stem cell therapy.However,how stem cells perceive the topological differences between them to regulate cell function remains to be unclear.Here,we systematically studied the changes in stem cell function under the action of MPs and PMPs and elucidated the related mechanisms.Our findings show that the porous structure of PMPs can be sensed by focal adhesions(FAs),which triggers the synthesis of F-actin to inhibit the phosphorylation and degradation of Yes-associated protein(YAP),while also transmitting stress to the nucleus through the contraction of F-actin,thereby enhancing the nuclear translocation of YAP protein.The activation of YAP significantly enhances the proliferation,osteogenesis,paracrine and glucose metabolism of BMSCs,making them exhibit stronger bone repair ability in both in vivo and in vitro experiments.In summary,this study provides a comprehensive and reliable understanding of the behavior of BMSCs in response to MPs and PMPs.It also deepens our understanding of the association between microparticles’topological cues and biological functions,which will provide valuable guidance for the construction of bone tissue engineering(BTE)scaffolds.
文摘Mechanotransduction is the process that enables the conversion of mechanical cues into biochemical signaling.While all our cells are well known to be sensitive to such stimuli,the details of the systemic interaction between mechanical input and inflammation are not well integrated.Often,indeed,they are considered and studied in relatively compartmentalized areas,and we therefore argue here that to understand the relationship of mechanical stimuli with inflammation-with a high translational potential-it is crucial to offer and analyze a unified view of mechanotransduction.We therefore present here pathway representation,recollected with the standard systems biology markup language(SBML)and explored with network biology approaches,offering RAC1 as an exemplar and emerging molecule with potential for medical translation.
基金supported by the National Research Foundation of Korea(2022R1A2C3007730,2021M3A9I2080493 and RS-2023-00217798)the Korea-US Collaborative Research Fund(RS-2024-00468455)funded by the Ministry of Science and ICT and the Ministry of Health&Welfare,Republic of Korea.
文摘Group 2 innate lymphoid cells(ILC2s)are central effectors of type 2 immune responses in the lung;however,how mechanical cues regulate their function remains unclear.Here,we identified the mechanosensitive ion channel Piezo1 as a key regulator of ILC2 effector function through translational control.Piezo1 is highly expressed in murine and human ILC2s,and its activation by mechanical stress or the Piezo1 agonist,Yoda1 induces calcium influx,triggering mTOR signaling and selectively enhancing IL-13 protein production.Conditional deletion of Piezo1 in ILC2s reduced mTOR activation and puromycin incorporation,leading to impaired protein synthesis and attenuated lung inflammation and fibrosis in the IL-33,Alternaria alternata,and bleomycin models.scRNA-seq and scATAC-seq confirmed that Piezo1-deficient ILC2s retained Il13 transcription and chromatin accessibility but presented translational suppression,as evidenced by protein‒mRNA interactions.Pharmacologic mTOR inhibition phenocopied Piezo1 loss,supporting the functional relevance of the Piezo1–mTOR axis.These findings demonstrate that Piezo1 functions as a mechanosensor that integrates biomechanical cues to regulate cytokine output via mTOR-mediated translation.Targeting Piezo1 signaling or its downstream effectors may provide therapeutic benefits in type 2 inflammation–associated lung diseases.
