Sirt1 inhibits renal tubular cell epithelial-mesenchymal transition through YY1 deacetylation in diabetic nephropathy

• 来源期刊: 中国药理学报（英文版）
• 年，卷（期）: 2021,（2）
• 所属期刊栏目: Renal Pharmacology
• 页码范围: 242-251
• 页数: 10页
• 语种: 英文
• DOI: 10.1038/s41401-020-0450-2

摘要

Silent information regulator 1(Sirt1)is a deacetylase,which plays an important role in the occurrence and development of diabetic nephropathy(DN).Our previous study shows that Yin yang 1(YY1),a widely expressed zinc finger DNA/RNA-binding transcription factor,is a novel regulator of renal fibrosis in diabetic nephropathy.Since the activity of YY1 is regulated via acetylation and deacetylation modification,this study aimed to explore whether Sirt1-induced deacetylation of YY1 mediated high glucose(HG)-induced renal tubular epithelial-mesenchymal transition(EMT)and renal fibrosis in vivo and in vitro.We first confirmed that Sirt1 expression level was significantly decreased in the kidney of db/db mice and in HG-treated HK-2 cells.Diabetes-induced Sirt1 reduction enhanced the level of YY1 acetylation and renal tubular EMT.Then,we manipulated Sirt1 expression in vivo and in vitro by injecting resveratrol(50 mg·kg-1·d-1·ip)to db/db mice for 2 weeks or application of SRT1720(2.5 μM)in HG-treated HK-2 cells,we found that activation of Sirt1 reversed the renal tubular EMT and YY1 acetylation induced by HG condition.On the contrary,Sirt1 was knocked down in db/m mice or EX527(1 μM)was added in HK-2 cells,we found that inhibition of Sirt1 exacerbated renal fibrosis in diabetic mice and enhanced level of YY1 acetylation in HK-2 cells.Furthermore,knockdown of YY1 inhibited the ameliorating effect of resveratrol on renal tubular EMT and renal fibrosis in db/db mice.In conclusion,this study demonstrates that Sirt1 plays an important role in renal tubular EMT of DN through mediating deacetylation of YY1.