Tissue inhibitor of m etalloprotease-1(TIM P-1)is a tissue inhibitor o f matrix metalloproteinases(MMPs).It however exerts multiple effects on biological processes,such as cell growth,proliferation,differentiation and...Tissue inhibitor of m etalloprotease-1(TIM P-1)is a tissue inhibitor o f matrix metalloproteinases(MMPs).It however exerts multiple effects on biological processes,such as cell growth,proliferation,differentiation and apoptosis,in an MMP-independent manner.This study aimed to examine the role of TIMP-1 in adipogenesis of adipose-derived stem cells(ASCs)and the underlying mechanism.We knocked down the TIMP-1 gene in ASCs through lentiviral vectors encoding TIMP-1 small interfering RNA(siRNA),and then found that the knockdown of TIMP-1 in ASCs promoted the adipogenic differentiation of stem cells and inhibited the Wnt/β-catenin signaling pathway in ASCs.We also noted that mutant TIMP-1 without the inhibitory activity on MMPs promoted the activation of Wnt/β-catenin pathway as well as the recombinant wild type TIMP-1 did,which indicated that the effect of TIMP-1 on Wnt/β-catenin pathway was MMPindependent.Our study suggested that TIMP-1 negatively regulated the adipogenesis of ASCs via the Wnt/β-catenin signaling pathway in an MMP-independent manner.展开更多
Diabetic cardiomyopathy(DCM)is one of the major heart complications of diabetic patients.Hydrogen sulfide(H2S)is now recognized as an important signaling molecule and has been shown to attenuate the development of dia...Diabetic cardiomyopathy(DCM)is one of the major heart complications of diabetic patients.Hydrogen sulfide(H2S)is now recognized as an important signaling molecule and has been shown to attenuate the development of diabetic cardiomyopathy.However,the underlying mechanisms linking H2S and the development of DCM have not been fully elucidated.In the present study,we therefore sought to explore the role and mechanism of H2S in the pathogenesis of DCM by establishing high glucose-induced injury model in neonatal rat cardiomyocytes(NRCMs)and H9c2 cells.Using cystathionine gamma-lyase(CSE)overexpression and CSE interference vectors transfection,the cell viability,cell apoptosis,and oxidative stress were determined and compared between the treatment of high glucose induction and exgenous NaHS administration.Meanwhile,the relationship between the CSE/H2S system and Wnt/beta-catenin pathway was analyzed and discussed in the high glucose-induced cardiomyocytes.Our results indicated that H2S played an important protective role in high glucose-induced apoptosis and oxidative stress in cardiomyocytes,as shown by the decreased reactive oxygen species and malondialdehyde levels,and the increased activities of superoxide dismutase,catalase and glutathione peroxidase.Moreover,H:S could attenuate the Wnt/p-catenin signalling pathway and up-regulate the expression of haem oxygenase-1(HO-1)and NAD(P)H:quinone oxidoreductase 1(NQOl)in the diabetic myocardium cells.Together,these results demonstrated that H2S could attenuate high glucoseinduced myocardial injury in rat cardiomyocytes by suppressing Wnt/p-catenin pathway.展开更多
文摘Tissue inhibitor of m etalloprotease-1(TIM P-1)is a tissue inhibitor o f matrix metalloproteinases(MMPs).It however exerts multiple effects on biological processes,such as cell growth,proliferation,differentiation and apoptosis,in an MMP-independent manner.This study aimed to examine the role of TIMP-1 in adipogenesis of adipose-derived stem cells(ASCs)and the underlying mechanism.We knocked down the TIMP-1 gene in ASCs through lentiviral vectors encoding TIMP-1 small interfering RNA(siRNA),and then found that the knockdown of TIMP-1 in ASCs promoted the adipogenic differentiation of stem cells and inhibited the Wnt/β-catenin signaling pathway in ASCs.We also noted that mutant TIMP-1 without the inhibitory activity on MMPs promoted the activation of Wnt/β-catenin pathway as well as the recombinant wild type TIMP-1 did,which indicated that the effect of TIMP-1 on Wnt/β-catenin pathway was MMPindependent.Our study suggested that TIMP-1 negatively regulated the adipogenesis of ASCs via the Wnt/β-catenin signaling pathway in an MMP-independent manner.
基金the Natural Science Foundation of Hubei Province of China(No.2011CDC146).
文摘Diabetic cardiomyopathy(DCM)is one of the major heart complications of diabetic patients.Hydrogen sulfide(H2S)is now recognized as an important signaling molecule and has been shown to attenuate the development of diabetic cardiomyopathy.However,the underlying mechanisms linking H2S and the development of DCM have not been fully elucidated.In the present study,we therefore sought to explore the role and mechanism of H2S in the pathogenesis of DCM by establishing high glucose-induced injury model in neonatal rat cardiomyocytes(NRCMs)and H9c2 cells.Using cystathionine gamma-lyase(CSE)overexpression and CSE interference vectors transfection,the cell viability,cell apoptosis,and oxidative stress were determined and compared between the treatment of high glucose induction and exgenous NaHS administration.Meanwhile,the relationship between the CSE/H2S system and Wnt/beta-catenin pathway was analyzed and discussed in the high glucose-induced cardiomyocytes.Our results indicated that H2S played an important protective role in high glucose-induced apoptosis and oxidative stress in cardiomyocytes,as shown by the decreased reactive oxygen species and malondialdehyde levels,and the increased activities of superoxide dismutase,catalase and glutathione peroxidase.Moreover,H:S could attenuate the Wnt/p-catenin signalling pathway and up-regulate the expression of haem oxygenase-1(HO-1)and NAD(P)H:quinone oxidoreductase 1(NQOl)in the diabetic myocardium cells.Together,these results demonstrated that H2S could attenuate high glucoseinduced myocardial injury in rat cardiomyocytes by suppressing Wnt/p-catenin pathway.
