Diabetic retinopathy(DR),a leading cause of visual loss,is the result of microvascular damage induced by prolonged hyperglycemia.Numerous studies have revealed the pivotal role of integrins in the pathogenesis of DR,p...Diabetic retinopathy(DR),a leading cause of visual loss,is the result of microvascular damage induced by prolonged hyperglycemia.Numerous studies have revealed the pivotal role of integrins in the pathogenesis of DR,particularly in key processes such as inflammation,vascular leakage,microthrombus formation,and angiogenesis.Consequently,targeting integrins is considered a promising strategy for the treatment of DR.This review focuses on the function of integrins in DR and their potential as therapeutic targets.It describes the molecular mechanisms through which integrins influence DR progression and summarizes the latest outcomes of integrin antagonist-based therapeutic strategies in clinical studies,evaluating their efficacy and potential challenges,which offer promise as novel treatment options for DR.展开更多
Salmonella enterica serovar Typhimurium,the causative agent of gastroenteritis,is one of the most successful intracellular pathogens.Although certain host factors for Salmonella infection have been unveiled,the factor...Salmonella enterica serovar Typhimurium,the causative agent of gastroenteritis,is one of the most successful intracellular pathogens.Although certain host factors for Salmonella infection have been unveiled,the factors mediating Salmonella entry,particularly the invasion process,remain obscure.Here,we have unearthed β2 integrin,a crucial member of the integrin family,as an important host factor facilitating Salmonella invasion.It is demonstrated that overexpression of β2 integrin promotes Salmonella invasion,while the knockdown of β2 integrin significantly diminishes the extent of invasion.Moreover,Salmonella exhibits specific binding affinity towards β2 integrin,and the block of β2 integrin on cell surface substantially reduces the infection of cells in vitro.The ectodomain soluble protein of β2 integrin neutralized Salmonella infection both in cells(in vitro)and in mice(in vivo).Additionally,Salmonella protein YrbD directly interacts with β2 integrin to facilitate its invasion.To our knowledge,this study showed for the first time that the protein YrbD mediates Salmonella adhesion and internalization into host cells by interacting with β2 integrin.These findings not only broaden our understanding of the mechanisms underlying Salmonella entry,but also identify a prospective target for therapeutic control.展开更多
Integrins are heterodimeric transmembrane receptors that mediate bidirectional interactions between the intracellular cytoskeletal array and the extracellularmatrix.These interactions are critical in tissue developmen...Integrins are heterodimeric transmembrane receptors that mediate bidirectional interactions between the intracellular cytoskeletal array and the extracellularmatrix.These interactions are critical in tissue development and function by regulating gene expression and sustaining tissue architecture.In humans,the integrin family is composed of 18 alpha(α)and 8 beta(β)subunits,constituting 24 distinctαβcombinations.Based on their structure and ligandbinding properties,only a subset of integrins,8 out of 24,recognizes the arginine-glycine-aspartate(RGD)tripeptide motif in the native ligand.One of the major RGD binding integrins is integrin alpha 8 beta 1(α8β1),a central Ras homolog gene familymemberA(RHOA)-dependentmodulator highly expressed in cells with contractile function.This review focuses on the recent advances regardingα8β1 function during organ development,with a particular interest in kidney and inner ear development.We alsodiscussα8β1’s role ininjury anddisease and its importance formesenchymal to epithelial transition during cancer development.Finally,we highlightα8β1’s importance for hearing function and its future use as a potential diagnostic and therapeutic tool for disease elimination.展开更多
Integrins are a highly complex family of receptors that, when expressed on the surface of cells, can mediate reciprocal cell-to-cell and cell-to-extracellular matrix(ECM) interactions leading to assembly of integrin a...Integrins are a highly complex family of receptors that, when expressed on the surface of cells, can mediate reciprocal cell-to-cell and cell-to-extracellular matrix(ECM) interactions leading to assembly of integrin adhesion complexes(IACs) that initiate many signaling functions both at the membrane and deeper within the cytoplasm to coordinate processes including cell adhesion, migration, proliferation, survival, differentiation, and metabolism. All metazoan organisms possess integrins, and it is generally agreed that integrins were associated with the evolution of multicellularity, being essential for the association of cells with their neighbors and surroundings, during embryonic development and many aspects of cellular and molecular biology. Integrins have important roles in many aspects of embryonic development, normal physiology, and disease processes with a multitude of functions discovered and elucidated for integrins that directly influence many areas of biology and medicine, including mammalian pregnancy, in particular implantation of the blastocyst to the uterine wall, subsequent placentation and conceptus(embryo/fetus and associated placental membranes) development. This review provides a succinct overview of integrin structure, ligand binding, and signaling followed with a concise overview of embryonic development, implantation, and early placentation in pigs, sheep, humans, and mice as an example for rodents. A brief timeline of the initial localization of integrin subunits to the uterine luminal epithelium(LE) and conceptus trophoblast is then presented, followed by sequential summaries of integrin expression and function during gestation in pigs, sheep, humans, and rodents. As appropriate for this journal, summaries of integrin expression and function during gestation in pigs and sheep are in depth, whereas summaries for humans and rodents are brief. Because similar models to those illustrated in Fig. 1, 2, 3, 4, 5 and 6 are present throughout the scientific literature, the illustrations in this manuscript are drafted as Viking imagery for entertainment purposes.展开更多
OBJECTIVE: To investigate the mechanism of Bushen Huoxue decoction( 补肾活血汤, BSHXD) to treat endometriosis-induced infertility. MEDHODS: The main compounds of BSHXD were determined by high performance liquid chroma...OBJECTIVE: To investigate the mechanism of Bushen Huoxue decoction( 补肾活血汤, BSHXD) to treat endometriosis-induced infertility. MEDHODS: The main compounds of BSHXD were determined by high performance liquid chromatographymass spectrometry(HPLC-MS/MS). The effect of BSHXD on Homeobox A10(HOXA10) and alpha(v)beta(3)(αvβ3) integrin expression of Ishikawa cells, mouse model, and endometriosis-associated infertility women was evaluated by using Western blot analysis, immunohistochemistry and Real-Time quantitative polymerase chain reaction(RTq PCR). The efficacy of BSHXD on embryo attachment were examined by using the Be Wo spheroid and mouse embryo attachment assay. HOXA10 concentration in uterine flushing fluid of endometriosis-associated infertility women treated with BSHXD was measured by EnzymeLinked immunosorbent assay(ELISA).RESULTS: BSHXD improved Be Wo spheroid and mice blastocysts attachment to Ishikawa cells and increased embryo implantation rates in mice and pregnancy rates in women with endometriosis-associated infertility. BSHXD enhanced HOXA10 and αvβ3 integrin expression in Ishikawa cell, endometriosis mouse model, and endometriosis-associated infertility women, which potentially improved endometrial receptivity. CONCLUSIONS: BSHXD could improve endometrial receptivity of endometriosis-associated infertility in a dosedependent manner by regulating HOXA10 and αvβ3 integrin expression.展开更多
BACKGROUND Non-invasive methods to diagnose non-alcoholic steatohepatitis(NASH),an inflammatory subtype of non-alcoholic fatty liver disease(NAFLD),are currently unavailable.AIM To develop an integrin αvβ3-targeted ...BACKGROUND Non-invasive methods to diagnose non-alcoholic steatohepatitis(NASH),an inflammatory subtype of non-alcoholic fatty liver disease(NAFLD),are currently unavailable.AIM To develop an integrin αvβ3-targeted molecular imaging modality to differentiate NASH.METHODS Integrinαvβ3 expression was assessed in Human LO2 hepatocytes Scultured with palmitic and oleic acids(FFA).Hepatic integrinαvβ3 expression was analyzed in rabbits fed a high-fat diet(HFD)and in rats fed a high-fat,high-carbohydrate diet(HFCD).After synthesis,cyclic arginine-glycine-aspartic acid peptide(cRGD)was labeled with gadolinium(Gd)and used as a contrast agent in magnetic resonance imaging(MRI)performed on mice fed with HFCD.RESULTS Integrin αvβ3 was markedly expressed on FFA-cultured hepatocytes,unlike the control hepatocytes.Hepatic integrin αvβ3 expression significantly increased in both HFD-fed rabbits and HFCD-fed rats as simple fatty liver(FL)progressed to steatohepatitis.The distribution of integrinαvβ3 in the liver of NASH cases largely overlapped with albumin-positive staining areas.In comparison to mice with simple FL,the relative liver MRI-T1 signal value at 60 minutes post-injection of Gd-labeled cRGD was significantly increased in mice with steatohepatitis(P<0.05),showing a positive correlation with the NAFLD activity score(r=0.945;P<0.01).Hepatic integrin αvβ3 expression was significantly upregulated during NASH development,with hepatocytes being the primary cells expressing integrin αvβ3.CONCLUSION After using Gd-labeled cRGD as a tracer,NASH was successfully distinguished by visualizing hepatic integrin αvβ3 expression with MRI.展开更多
Integrin β4 (ITGB4) is emerging as a pivotal player in breast cancer progression, particularly in aggressive and invasive subtypes such as triple-negative breast cancer (TNBC). This review broadly summarizes current ...Integrin β4 (ITGB4) is emerging as a pivotal player in breast cancer progression, particularly in aggressive and invasive subtypes such as triple-negative breast cancer (TNBC). This review broadly summarizes current research on ITGB4’s involvement in breast cancer, focusing on its role in metastasis, metabolic reprogramming, drug resistance, and immunoregulation that collectively influence tumor behavior with implications for the development of innovative and more efficacious therapeutic modalities.展开更多
AIM:To investigate the expressions of type I collagen, α2 integrin and β1 integrin in the posterior sclera of guinea pigs with defocus myopia and whether basic fibroblast growth factor (bFGF) injection inhibits the ...AIM:To investigate the expressions of type I collagen, α2 integrin and β1 integrin in the posterior sclera of guinea pigs with defocus myopia and whether basic fibroblast growth factor (bFGF) injection inhibits the formation and development of myopia by upregulating the expression of type I collagen, α2 integrin and β1 integrin. METHODS:After 14 days of treatment, the refractive state and axial length were measured and the levels of type I collagen, α2 integrin and β1 integrin were assayed in the posterior sclerae of groups of guinea pigs that wore a monocular-7D polymethylmethacrylate (PMMA) lens or had -7D lens wear followed by the peribulbar injection of Phosphate Buffer Solution (PBS) or bFGF. The untreated fellow eye served as a control. Guinea pigs with no treatment served as normal group. ·RESULTS:The results showed that 14 days of monocular defocus increased axial eye length and refraction, while bFGF delivery inhibited them markedly. Further, it was also found that the monocular-7D lens could decrease the levels of type I collagen, α2 integrin and β1 integrin expressions, while, unlike PBS, bFGF increased them significantly in comparison to contralateral control eyes and normal eyes. CONCLUSION:bFGF can prevent the formation anddevelopment of defocus myopia by upregulating the expressions of type I collagen, α2 integrin and β1 integrin. Taken together, our results demonstrate that bFGF promotes sclera remodeling to prevent myopia in guinea pigs.展开更多
基金Supported by the Natural Science Foundation of Inner Mongolia,No.2022MS080572022 Autonomous Region Medical and Health Science and Technology Plan Projects,No.202202190.
文摘Diabetic retinopathy(DR),a leading cause of visual loss,is the result of microvascular damage induced by prolonged hyperglycemia.Numerous studies have revealed the pivotal role of integrins in the pathogenesis of DR,particularly in key processes such as inflammation,vascular leakage,microthrombus formation,and angiogenesis.Consequently,targeting integrins is considered a promising strategy for the treatment of DR.This review focuses on the function of integrins in DR and their potential as therapeutic targets.It describes the molecular mechanisms through which integrins influence DR progression and summarizes the latest outcomes of integrin antagonist-based therapeutic strategies in clinical studies,evaluating their efficacy and potential challenges,which offer promise as novel treatment options for DR.
基金supported by the National Key R&D Program of China(2022YFF0710500)the the National Natural Science Foundation,China(31802192,32172853 and 32373013)+2 种基金the Natural Science Foundation of Heilongjiang Province of China(C2018070)China Postdoctoral Science Foundation(2017M620076)the Central Public-interest Scientific Institution Basal Research Fund,China(1610302022001)。
文摘Salmonella enterica serovar Typhimurium,the causative agent of gastroenteritis,is one of the most successful intracellular pathogens.Although certain host factors for Salmonella infection have been unveiled,the factors mediating Salmonella entry,particularly the invasion process,remain obscure.Here,we have unearthed β2 integrin,a crucial member of the integrin family,as an important host factor facilitating Salmonella invasion.It is demonstrated that overexpression of β2 integrin promotes Salmonella invasion,while the knockdown of β2 integrin significantly diminishes the extent of invasion.Moreover,Salmonella exhibits specific binding affinity towards β2 integrin,and the block of β2 integrin on cell surface substantially reduces the infection of cells in vitro.The ectodomain soluble protein of β2 integrin neutralized Salmonella infection both in cells(in vitro)and in mice(in vivo).Additionally,Salmonella protein YrbD directly interacts with β2 integrin to facilitate its invasion.To our knowledge,this study showed for the first time that the protein YrbD mediates Salmonella adhesion and internalization into host cells by interacting with β2 integrin.These findings not only broaden our understanding of the mechanisms underlying Salmonella entry,but also identify a prospective target for therapeutic control.
基金supported by NIH-NIDCD,5R01DC21070-0,and Creighton University’s Start-up funds to MZMs.Iman Ezzat was supported by the Department of Biomedical Sciences at Creighton University and the Bellucci Foundation pre-doctoral award.
文摘Integrins are heterodimeric transmembrane receptors that mediate bidirectional interactions between the intracellular cytoskeletal array and the extracellularmatrix.These interactions are critical in tissue development and function by regulating gene expression and sustaining tissue architecture.In humans,the integrin family is composed of 18 alpha(α)and 8 beta(β)subunits,constituting 24 distinctαβcombinations.Based on their structure and ligandbinding properties,only a subset of integrins,8 out of 24,recognizes the arginine-glycine-aspartate(RGD)tripeptide motif in the native ligand.One of the major RGD binding integrins is integrin alpha 8 beta 1(α8β1),a central Ras homolog gene familymemberA(RHOA)-dependentmodulator highly expressed in cells with contractile function.This review focuses on the recent advances regardingα8β1 function during organ development,with a particular interest in kidney and inner ear development.We alsodiscussα8β1’s role ininjury anddisease and its importance formesenchymal to epithelial transition during cancer development.Finally,we highlightα8β1’s importance for hearing function and its future use as a potential diagnostic and therapeutic tool for disease elimination.
基金supported by USDA-NRICGP 98-35203-6337 to FWB.and RCB,NRSA DHHS/NIH 1-F32-HDO 8501 O1A1 to GAJ,USDA-NRI 2006-35203-17199 to GAJ and Kayla J.BaylessUSDA National Institute of Food and Agriculture Research Initiative Competitive Fellowship Grant no.2012-67011-19892 to James W.Frank and GAJ+1 种基金Agriculture and Food Research Initiative Competitive Grant no.2016-67015-24955 from the USDA National Institute of Food and Agriculture to GAJ and FWBNational Institutes of Health Grant 1R21HD071468-01 to GAJ and KJB。
文摘Integrins are a highly complex family of receptors that, when expressed on the surface of cells, can mediate reciprocal cell-to-cell and cell-to-extracellular matrix(ECM) interactions leading to assembly of integrin adhesion complexes(IACs) that initiate many signaling functions both at the membrane and deeper within the cytoplasm to coordinate processes including cell adhesion, migration, proliferation, survival, differentiation, and metabolism. All metazoan organisms possess integrins, and it is generally agreed that integrins were associated with the evolution of multicellularity, being essential for the association of cells with their neighbors and surroundings, during embryonic development and many aspects of cellular and molecular biology. Integrins have important roles in many aspects of embryonic development, normal physiology, and disease processes with a multitude of functions discovered and elucidated for integrins that directly influence many areas of biology and medicine, including mammalian pregnancy, in particular implantation of the blastocyst to the uterine wall, subsequent placentation and conceptus(embryo/fetus and associated placental membranes) development. This review provides a succinct overview of integrin structure, ligand binding, and signaling followed with a concise overview of embryonic development, implantation, and early placentation in pigs, sheep, humans, and mice as an example for rodents. A brief timeline of the initial localization of integrin subunits to the uterine luminal epithelium(LE) and conceptus trophoblast is then presented, followed by sequential summaries of integrin expression and function during gestation in pigs, sheep, humans, and rodents. As appropriate for this journal, summaries of integrin expression and function during gestation in pigs and sheep are in depth, whereas summaries for humans and rodents are brief. Because similar models to those illustrated in Fig. 1, 2, 3, 4, 5 and 6 are present throughout the scientific literature, the illustrations in this manuscript are drafted as Viking imagery for entertainment purposes.
基金National Natural Science Foundation-funded Project:the Mechanism of Effect of Bushen Huoxue Decotion on Endometrial Receptivity in Endometriosis (No. 81603372)National Natural Science Foundation-funded Project:to Investigate the Mechanism of Bushen Huoxue Decoction in Improving Endometrial Receptivity Based on SUMOylation of Homeobox A10 (No. 82274190)Jiangsu Commission of Health Project:to Investigate the Mechanism of Bushen Huoxue Decoction in Improving Endometrial Receptivity Based on Leukemia Inhibitory Factor Signaling (No. M2022079)。
文摘OBJECTIVE: To investigate the mechanism of Bushen Huoxue decoction( 补肾活血汤, BSHXD) to treat endometriosis-induced infertility. MEDHODS: The main compounds of BSHXD were determined by high performance liquid chromatographymass spectrometry(HPLC-MS/MS). The effect of BSHXD on Homeobox A10(HOXA10) and alpha(v)beta(3)(αvβ3) integrin expression of Ishikawa cells, mouse model, and endometriosis-associated infertility women was evaluated by using Western blot analysis, immunohistochemistry and Real-Time quantitative polymerase chain reaction(RTq PCR). The efficacy of BSHXD on embryo attachment were examined by using the Be Wo spheroid and mouse embryo attachment assay. HOXA10 concentration in uterine flushing fluid of endometriosis-associated infertility women treated with BSHXD was measured by EnzymeLinked immunosorbent assay(ELISA).RESULTS: BSHXD improved Be Wo spheroid and mice blastocysts attachment to Ishikawa cells and increased embryo implantation rates in mice and pregnancy rates in women with endometriosis-associated infertility. BSHXD enhanced HOXA10 and αvβ3 integrin expression in Ishikawa cell, endometriosis mouse model, and endometriosis-associated infertility women, which potentially improved endometrial receptivity. CONCLUSIONS: BSHXD could improve endometrial receptivity of endometriosis-associated infertility in a dosedependent manner by regulating HOXA10 and αvβ3 integrin expression.
基金Supported by the National Natural Science Foundation of China,No.81670513and Young Scientists Fund of the National Natural Science Foundation of China,No.81900511。
文摘BACKGROUND Non-invasive methods to diagnose non-alcoholic steatohepatitis(NASH),an inflammatory subtype of non-alcoholic fatty liver disease(NAFLD),are currently unavailable.AIM To develop an integrin αvβ3-targeted molecular imaging modality to differentiate NASH.METHODS Integrinαvβ3 expression was assessed in Human LO2 hepatocytes Scultured with palmitic and oleic acids(FFA).Hepatic integrinαvβ3 expression was analyzed in rabbits fed a high-fat diet(HFD)and in rats fed a high-fat,high-carbohydrate diet(HFCD).After synthesis,cyclic arginine-glycine-aspartic acid peptide(cRGD)was labeled with gadolinium(Gd)and used as a contrast agent in magnetic resonance imaging(MRI)performed on mice fed with HFCD.RESULTS Integrin αvβ3 was markedly expressed on FFA-cultured hepatocytes,unlike the control hepatocytes.Hepatic integrin αvβ3 expression significantly increased in both HFD-fed rabbits and HFCD-fed rats as simple fatty liver(FL)progressed to steatohepatitis.The distribution of integrinαvβ3 in the liver of NASH cases largely overlapped with albumin-positive staining areas.In comparison to mice with simple FL,the relative liver MRI-T1 signal value at 60 minutes post-injection of Gd-labeled cRGD was significantly increased in mice with steatohepatitis(P<0.05),showing a positive correlation with the NAFLD activity score(r=0.945;P<0.01).Hepatic integrin αvβ3 expression was significantly upregulated during NASH development,with hepatocytes being the primary cells expressing integrin αvβ3.CONCLUSION After using Gd-labeled cRGD as a tracer,NASH was successfully distinguished by visualizing hepatic integrin αvβ3 expression with MRI.
文摘Integrin β4 (ITGB4) is emerging as a pivotal player in breast cancer progression, particularly in aggressive and invasive subtypes such as triple-negative breast cancer (TNBC). This review broadly summarizes current research on ITGB4’s involvement in breast cancer, focusing on its role in metastasis, metabolic reprogramming, drug resistance, and immunoregulation that collectively influence tumor behavior with implications for the development of innovative and more efficacious therapeutic modalities.
文摘AIM:To investigate the expressions of type I collagen, α2 integrin and β1 integrin in the posterior sclera of guinea pigs with defocus myopia and whether basic fibroblast growth factor (bFGF) injection inhibits the formation and development of myopia by upregulating the expression of type I collagen, α2 integrin and β1 integrin. METHODS:After 14 days of treatment, the refractive state and axial length were measured and the levels of type I collagen, α2 integrin and β1 integrin were assayed in the posterior sclerae of groups of guinea pigs that wore a monocular-7D polymethylmethacrylate (PMMA) lens or had -7D lens wear followed by the peribulbar injection of Phosphate Buffer Solution (PBS) or bFGF. The untreated fellow eye served as a control. Guinea pigs with no treatment served as normal group. ·RESULTS:The results showed that 14 days of monocular defocus increased axial eye length and refraction, while bFGF delivery inhibited them markedly. Further, it was also found that the monocular-7D lens could decrease the levels of type I collagen, α2 integrin and β1 integrin expressions, while, unlike PBS, bFGF increased them significantly in comparison to contralateral control eyes and normal eyes. CONCLUSION:bFGF can prevent the formation anddevelopment of defocus myopia by upregulating the expressions of type I collagen, α2 integrin and β1 integrin. Taken together, our results demonstrate that bFGF promotes sclera remodeling to prevent myopia in guinea pigs.
