In the early stages of traumatic spinal cord injury,extensive accumulation of autophagosomes creates a neurotoxic microenvironment,exacerbating neuronal cell death and worsening tissue damage,ultimately hindering neur...In the early stages of traumatic spinal cord injury,extensive accumulation of autophagosomes creates a neurotoxic microenvironment,exacerbating neuronal cell death and worsening tissue damage,ultimately hindering neurofunctional recovery.Activin A is a critical growth factor necessary for the development of the embryonic nervous system and for maintaining neuronal function in the adult cerebral cortex.It can inhibit excessive autophagy in ischemic stroke to reduce neuronal damage.However,the specific mechanism through which Activin A functions in the spinal cord remains poorly understood.In this study,we administered different concentrations of Activin A to neural stem cells from the spinal cord and found that Activin A stimulated the proliferation and neuronal differentiation of neural stem cells.Then,we established an in vitro oxidative stress model by using hydrogen peroxide to stimulate the neural stem cells-induced neurons.We found that Activin A could reduce apoptosis caused by oxidative stress.Subsequently,we treated a mouse model of spinal cord contusion with intrathecal injection of Activin A.Behavioral and electrophysiological results showed that Activin A promoted recovery of motor function and reconstruction of neural circuits in the model mice.Finally,RNA sequencing indicated that Activin A inhibited autophagy by activating the PI3K/AKT/mTOR pathway and upregulating the expression of synaptogenesis-related factor Sema3A in the spinal cord.These results suggest that Activin A may mediate the excessive autophagic response after spinal cord injury,promote the reconstruction of damaged neural circuits,and restore neurological function in the injured spinal cord.展开更多
BACKGROUND Transforming growth factor-β(TGF-β)superfamily plays an important role in tumor progression and metastasis.Activin A receptor type 1C(ACVR1C)is a TGF-βtype I receptor that is involved in tumorigenesis th...BACKGROUND Transforming growth factor-β(TGF-β)superfamily plays an important role in tumor progression and metastasis.Activin A receptor type 1C(ACVR1C)is a TGF-βtype I receptor that is involved in tumorigenesis through binding to dif-ferent ligands.AIM To evaluate the correlation between single nucleotide polymorphisms(SNPs)of ACVR1C and susceptibility to esophageal squamous cell carcinoma(ESCC)in Chinese Han population.METHODS In this hospital-based cohort study,1043 ESCC patients and 1143 healthy controls were enrolled.Five SNPs(rs4664229,rs4556933,rs77886248,rs77263459,rs6734630)of ACVR1C were assessed by the ligation detection reaction method.Hardy-Weinberg equilibrium test,genetic model analysis,stratified analysis,linkage disequi-librium test,and haplotype analysis were conducted.RESULTS Participants carrying ACVR1C rs4556933 GA mutant had significantly decreased risk of ESCC,and those with rs77886248 TA mutant were related with higher risk,especially in older male smokers.In the haplotype analysis,ACVR1C Trs4664229Ars4556933Trs77886248Crs77263459Ars6734630 increased risk of ESCC,while Trs4664229Grs4556933Trs77886248Crs77263459Ars6734630 was associated with lower susceptibility to ESCC.CONCLUSION ACVR1C rs4556933 and rs77886248 SNPs were associated with the susceptibility to ESCC,which could provide a potential target for early diagnosis and treatment of ESCC in Chinese Han population.展开更多
Lin et al’s investigation on the association of activin A receptor type 1C(ACVR1C)(transforming growth factor beta type I receptor)single nucleotide poly-morphisms(SNPs)with esophageal squamous cell carcinoma(ESCC)ri...Lin et al’s investigation on the association of activin A receptor type 1C(ACVR1C)(transforming growth factor beta type I receptor)single nucleotide poly-morphisms(SNPs)with esophageal squamous cell carcinoma(ESCC)risk in the Chinese population is a scientific approach.This study explores the susceptibility of ACVR1C polymorphism towards ESCC in the Chinese population,highlighting the polymorphism’s potentiality as an early diagnostic and therapeutic target.The author assessed about a thousand ESCC Chinese patients’samples for ACVR1C SNPs in a hospital-based cohort study using the ligation detection reaction method.Further,the hypothesis was tested using appropriate statistical genetic models and stratified analysis.ACVR1C SNPs can help assess ESCC susceptibility stratification and provide valuable information for individual diagnosis and treatment of ESCC patients.In order to account for confounding variables,find genuine SNP-disease relationships,boost statistical power,and make biological interpretation easier,it is imperative that genetic association studies of ESCC incorporate pertinent clinical aspects.展开更多
Regulation of the number of aetivin receptors that are present in the cell membrane plays a key role in the modulation of cellular responses to activin. In order to find the regulators, a novel protein ARIPzip, intera...Regulation of the number of aetivin receptors that are present in the cell membrane plays a key role in the modulation of cellular responses to activin. In order to find the regulators, a novel protein ARIPzip, interacting with activin type II receptors, was searched and identified by using yeast two-hybrid screening. ARIPzip is a splicing variant of ARIP2. This has been discussed previously. ARIPzip can specifically interact with ActR Ⅱ A, and is widely distributed in mouse tissues. Overexpression of ARIPzip can cause the activin-induced transcriptional activities to increase in a dose-dependent manner while the overexpression of ARIV2 can decrease these activities. These data suggest that the C-terminal rezions of ARIP2 and ARIPzip are involved in the regulation of activin signaling.展开更多
In this study, PC12 cells were induced to differentiate into neuron-like cells using nerve growth factor, and were subjected to oxygen-glucose deprivation. Cells were treated with 0, 10, 20, 30, 50, 100 ng/mL exogenou...In this study, PC12 cells were induced to differentiate into neuron-like cells using nerve growth factor, and were subjected to oxygen-glucose deprivation. Cells were treated with 0, 10, 20, 30, 50, 100 ng/mL exogenous Activin A. The 3-（4,5-dimethyl-2-thiazolyl）-2,5-diphenyl tetrazolium bromide assay and Hoechst 33324 staining showed that the survival percentage of PC12 cells significantly decreased and the rate of apoptosis significantly increased after oxygen-glucose deprivation. Exogenous Activin A significantly increased the survival percentage of PC12 cells in a dose-dependent manner. Reverse transcription-PCR results revealed a significant increase in Activin receptor IIA, Smad3 and Smad4 mRNA levels, which are key sites in the Activin A/Smads signaling pathway, in neuron-like cells subjected to oxygen-glucose deprivation, while mRNA expression of the apoptosis-regulation gene caspase-3 decreased. Our experimental findings indicate that exogenous Activin A plays an anti-apoptotic role and protects neurons by means of activating the Activin A/Smads signaling pathway.展开更多
基金supported by the National Natural Science Foundation of China,Nos.82271419,81901902(to YZ),82202702(to ZW),82202351(to XH),82301550(to LYang),82271418(to XX)the Shanghai Rising-Star Program,No.22QA1408200(to YZ)the Fundamental Research Fundsfor the Central Universities,No.22120220555(to YZ).
文摘In the early stages of traumatic spinal cord injury,extensive accumulation of autophagosomes creates a neurotoxic microenvironment,exacerbating neuronal cell death and worsening tissue damage,ultimately hindering neurofunctional recovery.Activin A is a critical growth factor necessary for the development of the embryonic nervous system and for maintaining neuronal function in the adult cerebral cortex.It can inhibit excessive autophagy in ischemic stroke to reduce neuronal damage.However,the specific mechanism through which Activin A functions in the spinal cord remains poorly understood.In this study,we administered different concentrations of Activin A to neural stem cells from the spinal cord and found that Activin A stimulated the proliferation and neuronal differentiation of neural stem cells.Then,we established an in vitro oxidative stress model by using hydrogen peroxide to stimulate the neural stem cells-induced neurons.We found that Activin A could reduce apoptosis caused by oxidative stress.Subsequently,we treated a mouse model of spinal cord contusion with intrathecal injection of Activin A.Behavioral and electrophysiological results showed that Activin A promoted recovery of motor function and reconstruction of neural circuits in the model mice.Finally,RNA sequencing indicated that Activin A inhibited autophagy by activating the PI3K/AKT/mTOR pathway and upregulating the expression of synaptogenesis-related factor Sema3A in the spinal cord.These results suggest that Activin A may mediate the excessive autophagic response after spinal cord injury,promote the reconstruction of damaged neural circuits,and restore neurological function in the injured spinal cord.
基金Supported by The National Natural Science Foundation of China,No.82350127 and No.82241013the Shanghai Natural Science Foundation,No.20ZR1411600+2 种基金the Shanghai Shenkang Hospital Development Center,No.SHDC2020CR4039the Bethune Ethicon Excellent Surgery Foundation,No.CESS2021TC04Xuhui District Medical Research Project of Shanghai,No.SHXH201805.
文摘BACKGROUND Transforming growth factor-β(TGF-β)superfamily plays an important role in tumor progression and metastasis.Activin A receptor type 1C(ACVR1C)is a TGF-βtype I receptor that is involved in tumorigenesis through binding to dif-ferent ligands.AIM To evaluate the correlation between single nucleotide polymorphisms(SNPs)of ACVR1C and susceptibility to esophageal squamous cell carcinoma(ESCC)in Chinese Han population.METHODS In this hospital-based cohort study,1043 ESCC patients and 1143 healthy controls were enrolled.Five SNPs(rs4664229,rs4556933,rs77886248,rs77263459,rs6734630)of ACVR1C were assessed by the ligation detection reaction method.Hardy-Weinberg equilibrium test,genetic model analysis,stratified analysis,linkage disequi-librium test,and haplotype analysis were conducted.RESULTS Participants carrying ACVR1C rs4556933 GA mutant had significantly decreased risk of ESCC,and those with rs77886248 TA mutant were related with higher risk,especially in older male smokers.In the haplotype analysis,ACVR1C Trs4664229Ars4556933Trs77886248Crs77263459Ars6734630 increased risk of ESCC,while Trs4664229Grs4556933Trs77886248Crs77263459Ars6734630 was associated with lower susceptibility to ESCC.CONCLUSION ACVR1C rs4556933 and rs77886248 SNPs were associated with the susceptibility to ESCC,which could provide a potential target for early diagnosis and treatment of ESCC in Chinese Han population.
文摘Lin et al’s investigation on the association of activin A receptor type 1C(ACVR1C)(transforming growth factor beta type I receptor)single nucleotide poly-morphisms(SNPs)with esophageal squamous cell carcinoma(ESCC)risk in the Chinese population is a scientific approach.This study explores the susceptibility of ACVR1C polymorphism towards ESCC in the Chinese population,highlighting the polymorphism’s potentiality as an early diagnostic and therapeutic target.The author assessed about a thousand ESCC Chinese patients’samples for ACVR1C SNPs in a hospital-based cohort study using the ligation detection reaction method.Further,the hypothesis was tested using appropriate statistical genetic models and stratified analysis.ACVR1C SNPs can help assess ESCC susceptibility stratification and provide valuable information for individual diagnosis and treatment of ESCC patients.In order to account for confounding variables,find genuine SNP-disease relationships,boost statistical power,and make biological interpretation easier,it is imperative that genetic association studies of ESCC incorporate pertinent clinical aspects.
文摘Regulation of the number of aetivin receptors that are present in the cell membrane plays a key role in the modulation of cellular responses to activin. In order to find the regulators, a novel protein ARIPzip, interacting with activin type II receptors, was searched and identified by using yeast two-hybrid screening. ARIPzip is a splicing variant of ARIP2. This has been discussed previously. ARIPzip can specifically interact with ActR Ⅱ A, and is widely distributed in mouse tissues. Overexpression of ARIPzip can cause the activin-induced transcriptional activities to increase in a dose-dependent manner while the overexpression of ARIV2 can decrease these activities. These data suggest that the C-terminal rezions of ARIP2 and ARIPzip are involved in the regulation of activin signaling.
基金supported by the Natural Science Foundation of Jilin Province, China, No. 201015181Jilin Province Science and Technology Development Projects, No.20120723
文摘In this study, PC12 cells were induced to differentiate into neuron-like cells using nerve growth factor, and were subjected to oxygen-glucose deprivation. Cells were treated with 0, 10, 20, 30, 50, 100 ng/mL exogenous Activin A. The 3-（4,5-dimethyl-2-thiazolyl）-2,5-diphenyl tetrazolium bromide assay and Hoechst 33324 staining showed that the survival percentage of PC12 cells significantly decreased and the rate of apoptosis significantly increased after oxygen-glucose deprivation. Exogenous Activin A significantly increased the survival percentage of PC12 cells in a dose-dependent manner. Reverse transcription-PCR results revealed a significant increase in Activin receptor IIA, Smad3 and Smad4 mRNA levels, which are key sites in the Activin A/Smads signaling pathway, in neuron-like cells subjected to oxygen-glucose deprivation, while mRNA expression of the apoptosis-regulation gene caspase-3 decreased. Our experimental findings indicate that exogenous Activin A plays an anti-apoptotic role and protects neurons by means of activating the Activin A/Smads signaling pathway.
