Systemic sclerosis(SSc)is characterized by immune dysfunction,vasculopathy,chronic fibrosis of skin and internal organs with complex etiology.With the rapid development and the application in biomedicine of epigenetic...Systemic sclerosis(SSc)is characterized by immune dysfunction,vasculopathy,chronic fibrosis of skin and internal organs with complex etiology.With the rapid development and the application in biomedicine of epigenetics,accumulating evidence has shown that epigenetics plays an important role in the pathogenesis of SSc.Environmental factors via epigenetics are needed to trigger and maintain for the disease in the subjects with genetic predisposition to SSc.The role of epigenetics in the pathogenesis of SSc includes hypermethylation of the promoter region of nitric oxide synthase and bone morphogenetic protein receptors II,up-regulation of histone deacetylases 4 and 5 expression,and down-regulation of miR-193b and miR-152 in endothelial cells inducing vascular dysfunction;DNA hypermethylation and hypoacetylation of histone H3 and H4 in Friend leukemia virus integration 1 and Kruppel-like factor 5 genes,and the abnormal expression of miR-29,miR-129-5p and miR-135b in fibroblasts causing excessive fibrosis;DNA hypomethylation in the promoter regions of CD11a and CD70 genes in CD4+T cells resulting in immune dysfunction.Studies on the role of epigenetics in SSc are of great significance for better understanding the pathogenic machanism of SSc,which is helpful to find new molecular targets for treating SSc,and consequently,improve the prognosis of SSc.展开更多
文摘Systemic sclerosis(SSc)is characterized by immune dysfunction,vasculopathy,chronic fibrosis of skin and internal organs with complex etiology.With the rapid development and the application in biomedicine of epigenetics,accumulating evidence has shown that epigenetics plays an important role in the pathogenesis of SSc.Environmental factors via epigenetics are needed to trigger and maintain for the disease in the subjects with genetic predisposition to SSc.The role of epigenetics in the pathogenesis of SSc includes hypermethylation of the promoter region of nitric oxide synthase and bone morphogenetic protein receptors II,up-regulation of histone deacetylases 4 and 5 expression,and down-regulation of miR-193b and miR-152 in endothelial cells inducing vascular dysfunction;DNA hypermethylation and hypoacetylation of histone H3 and H4 in Friend leukemia virus integration 1 and Kruppel-like factor 5 genes,and the abnormal expression of miR-29,miR-129-5p and miR-135b in fibroblasts causing excessive fibrosis;DNA hypomethylation in the promoter regions of CD11a and CD70 genes in CD4+T cells resulting in immune dysfunction.Studies on the role of epigenetics in SSc are of great significance for better understanding the pathogenic machanism of SSc,which is helpful to find new molecular targets for treating SSc,and consequently,improve the prognosis of SSc.
