标题：Histone deacetylase 4 selectively contributes to podocyte injury in diabetic nephropathy
作者：Xiaojie Wang;Jiang Liu;Junhui Zhen;Chun Zhang;Qiang Wan;G.uangyi Liu;Xinbing Wei;Yan Zhang;Ziying Wang;Huirong Han;Huiyan Xu;Cha
作者机构：[Wang, X] Department of Pharmacology, Shandong University School of Medicine, 44#, Wenhua Xi Road, Jinan, Shandong, 250012, China;[ Liu, J] Department 更多
通讯作者地址：[Yi, F]Shandong Univ, Sch Med, Dept Pharmacol, 44 Wenhua Xi Rd, Jinan 250012, Shandong, Peoples R China.
来源：Kidney International: Official Journal of the International Society of Nephrology
关键词：autophagy;diabetic complications;gene therapy;histone deacetylases;podocyte
摘要：Studies have highlighted the importance of histone deacetylase (HDAC)-mediated epigenetic processes in the development of diabetic complications. Inhibitors of HDAC are a novel class of therapeutic agents in diabetic nephropathy, but currently available inhibitors are mostly nonselective inhibit multiple HDACs, and different HDACs serve very distinct functions. Therefore, it is essential to determine the role of individual HDACs in diabetic nephropathy and develop HDAC inhibitors with improved specificity. First, we identified the expression patterns of HDACs and found that, among zinc-dependent HDACs, HDAC2/4/5 were upregulated in the kidney from streptozotocin-induced diabetic rats, diabetic db/db mice, and in kidney biopsies from diabetic patients. Podocytes treated with high glucose, advanced glycation end products, or transforming growth factor-p (common detrimental factors in diabetic nephropathy) selectively increased HDAC4 expression. The role of HDAC4 was evaluated by in vivo gene silencing by intrarenal lentiviral gene delivery and found to reduce renal injury in diabetic rats.