Purpose:The aim of this study was to investigate the potential of dynamic resistance exercise to generate skeletal muscle-derived follistatin like-1(FSTL1),which may induce cardioprotection in rats following myocardia...Purpose:The aim of this study was to investigate the potential of dynamic resistance exercise to generate skeletal muscle-derived follistatin like-1(FSTL1),which may induce cardioprotection in rats following myocardial infarction(MI)by inducing angiogenesis.Methods:Male,adult Sprague-Dawley rats were randomly divided into 5 groups(n=12 in each group):sham group(S),sedentary MI group(MI),MI+resistance exercise group(MR),MI+adeno-associated virus(AAV)-FSTL1 injection group(MA),and MI+AAV-FSTL1 injection+resistance exercise group(MAR).The AAV-FSTL1 vector was prepared by molecular biology methods and injected into the anterior tibialis muscle.The MI model was established by ligation of the left anterior descending coronary artery.Rats in the MR and MAR groups underwent 4 weeks of dynamic resistance exercise training using a weighted climbing-up ladder.Heart function was evaluated by hemodynamic measures.Collagen volume fraction of myocardium was observed and analyzed by Masson’s staining.Human umbilical vein vessel endothelial cells culture and recombinant human FSTL1 protein or transforming growth factor-b receptor 1(TGFbR1)inhibitor treatment were used to elucidate the molecular signaling mechanism of FSTL1.Angiogenesis,cell proliferation,and disco interacting protein 2 homolog A(DIP2A)location were observed by immunofluorescence staining.The expression of FSTL1,DIP2A,and the activation of signaling pathways were detected by Western blotting.Angiogenesis of endothelial cells was observed by tubule experiment.One-way analysis of variance and Student’s t test were used for statistical analysis.Results:Resistance exercise stimulated the secretion of skeletal muscle FSTL1,which promoted myocardial angiogenesis,inhibited pathological remodeling,and protected cardiac function in MI rats.Exercise facilitated skeletal muscle FSTL1 to play a role in protecting the heart.Exogenous FSTL1 promoted the human umbilical vein vessel endothelial cells proliferation and up-regulated the expression of DIP2A,while TGFbR1 inhibito展开更多
In many parts of the world hepatocellular carcinoma (HCC)is among the leading causes of cancer-related mortality but the underlying molecular pathology is still insufficiently understood.There is increasing evidence t...In many parts of the world hepatocellular carcinoma (HCC)is among the leading causes of cancer-related mortality but the underlying molecular pathology is still insufficiently understood.There is increasing evidence that activins,which are members of the transforming growth factorβ(TGFβ)superfamily of growth and differentiation factors,could play important roles in liver carcinogenesis.Activins are disulphide-linked homo- or heterodimers formed from four differentβsubunits termedβA,βB,βC,andβE,respectively.Activin A, the dimer of twoβA subunits,is critically involved in the regulation of cell growth,apoptosis,and tissue architecture in the liver,while the hepatic function of other activins is largely unexplored so far.Negative regulators of activin signals include antagonists in the extracellular space like the binding proteins follistatin and FLRG,and at the cell membrane antagonistic coreceptors like Cripto or BAMBI.Additionally,in the intracellular space inhibitory Smads can modulate and control activin activity.Accumulating data suggest that deregulation of activin signals contributes to pathologic conditions such as chronic inflammation,fibrosis and development of cancer.The current article reviews the alterations in components of the activin signaling pathway that have been observed in HCC and discusses their potential significance for liver tumorigenesis.展开更多
基金supported this research:The National Natural Science Foundation of China(No.31671240 to ZT,No.31900828 to YX).
文摘Purpose:The aim of this study was to investigate the potential of dynamic resistance exercise to generate skeletal muscle-derived follistatin like-1(FSTL1),which may induce cardioprotection in rats following myocardial infarction(MI)by inducing angiogenesis.Methods:Male,adult Sprague-Dawley rats were randomly divided into 5 groups(n=12 in each group):sham group(S),sedentary MI group(MI),MI+resistance exercise group(MR),MI+adeno-associated virus(AAV)-FSTL1 injection group(MA),and MI+AAV-FSTL1 injection+resistance exercise group(MAR).The AAV-FSTL1 vector was prepared by molecular biology methods and injected into the anterior tibialis muscle.The MI model was established by ligation of the left anterior descending coronary artery.Rats in the MR and MAR groups underwent 4 weeks of dynamic resistance exercise training using a weighted climbing-up ladder.Heart function was evaluated by hemodynamic measures.Collagen volume fraction of myocardium was observed and analyzed by Masson’s staining.Human umbilical vein vessel endothelial cells culture and recombinant human FSTL1 protein or transforming growth factor-b receptor 1(TGFbR1)inhibitor treatment were used to elucidate the molecular signaling mechanism of FSTL1.Angiogenesis,cell proliferation,and disco interacting protein 2 homolog A(DIP2A)location were observed by immunofluorescence staining.The expression of FSTL1,DIP2A,and the activation of signaling pathways were detected by Western blotting.Angiogenesis of endothelial cells was observed by tubule experiment.One-way analysis of variance and Student’s t test were used for statistical analysis.Results:Resistance exercise stimulated the secretion of skeletal muscle FSTL1,which promoted myocardial angiogenesis,inhibited pathological remodeling,and protected cardiac function in MI rats.Exercise facilitated skeletal muscle FSTL1 to play a role in protecting the heart.Exogenous FSTL1 promoted the human umbilical vein vessel endothelial cells proliferation and up-regulated the expression of DIP2A,while TGFbR1 inhibito
文摘In many parts of the world hepatocellular carcinoma (HCC)is among the leading causes of cancer-related mortality but the underlying molecular pathology is still insufficiently understood.There is increasing evidence that activins,which are members of the transforming growth factorβ(TGFβ)superfamily of growth and differentiation factors,could play important roles in liver carcinogenesis.Activins are disulphide-linked homo- or heterodimers formed from four differentβsubunits termedβA,βB,βC,andβE,respectively.Activin A, the dimer of twoβA subunits,is critically involved in the regulation of cell growth,apoptosis,and tissue architecture in the liver,while the hepatic function of other activins is largely unexplored so far.Negative regulators of activin signals include antagonists in the extracellular space like the binding proteins follistatin and FLRG,and at the cell membrane antagonistic coreceptors like Cripto or BAMBI.Additionally,in the intracellular space inhibitory Smads can modulate and control activin activity.Accumulating data suggest that deregulation of activin signals contributes to pathologic conditions such as chronic inflammation,fibrosis and development of cancer.The current article reviews the alterations in components of the activin signaling pathway that have been observed in HCC and discusses their potential significance for liver tumorigenesis.
