Long Zhao1, Xueling Wang1, Lina Sun1, Huibin Nie1, Xiangchun Liu1, Zhixin Chen1, Guangju Guan2. 1. Nephrology Research Institute, The Second Hospital of Shandong University, Shandong University, Jinan, People's Republic of China. 2. Nephrology Research Institute, The Second Hospital of Shandong University, Shandong University, Jinan, People's Republic of China guangj@sdu.edu.cn.
Abstract
PURPOSE: To investigate the expression and function of serum response factor in podocyte epithelial-mesenchymal transition of diabetic nephropathy. METHODS: The expression of serum response factor, epithelial markers and mesenchymal markers was examined in podocytes or renal cortex tissues following high glucose. Serum response factor was upregulated by its plasmids and downregulated by CCG-1423 to investigate how it influenced podocyte epithelial-mesenchymal transition in diabetic nephropathy. Streptozotocin was used to generate diabetes mellitus in rats. RESULTS: In podocytes after high glucose treatment, serum response factor and mesenchymal markers increased, while epithelial markers declined. Similar changes were observed in vivo. Serum response factor overexpression in podocytes induced expression of Snail, an important transcription factor mediating epithelial-mesenchymal transition. Blockade of serum response factor reduced Snail induction, protected podocytes from epithelial-mesenchymal transition and ameliorated proteinuria. CONCLUSION: Together, increased serum response factor activity provokes podocytes' epithelial-mesenchymal transition and dysfunction in diabetic nephropathy. Targeting serum response factor by small-molecule inhibitor may be an attractive therapeutic strategy for diabetic nephropathy.
PURPOSE: To investigate the expression and function of serum response factor in podocyte epithelial-mesenchymal transition of diabetic nephropathy. METHODS: The expression of serum response factor, epithelial markers and mesenchymal markers was examined in podocytes or renal cortex tissues following high glucose. Serum response factor was upregulated by its plasmids and downregulated by CCG-1423 to investigate how it influenced podocyte epithelial-mesenchymal transition in diabetic nephropathy. Streptozotocin was used to generate diabetes mellitus in rats. RESULTS: In podocytes after high glucose treatment, serum response factor and mesenchymal markers increased, while epithelial markers declined. Similar changes were observed in vivo. Serum response factor overexpression in podocytes induced expression of Snail, an important transcription factor mediating epithelial-mesenchymal transition. Blockade of serum response factor reduced Snail induction, protected podocytes from epithelial-mesenchymal transition and ameliorated proteinuria. CONCLUSION: Together, increased serum response factor activity provokes podocytes' epithelial-mesenchymal transition and dysfunction in diabetic nephropathy. Targeting serum response factor by small-molecule inhibitor may be an attractive therapeutic strategy for diabetic nephropathy.
Authors: Bing Guo; Qing Lyu; Orazio J Slivano; Ronald Dirkx; Christine K Christie; Jan Czyzyk; Aram F Hezel; Ali G Gharavi; Eric M Small; Joseph M Miano Journal: J Am Soc Nephrol Date: 2017-11-07 Impact factor: 10.121
Authors: Andrea Angeletti; Chiara Cantarelli; Astgik Petrosyan; Sofia Andrighetto; Kelly Budge; Vivette D D'Agati; Susan Hartzell; Deborah Malvi; Chiara Donadei; Joshua M Thurman; Danica Galešić-Ljubanović; John Cijiang He; Wenzhen Xiao; Kirk N Campbell; Jenny Wong; Clara Fischman; Joaquin Manrique; Gianluigi Zaza; Enrico Fiaccadori; Gaetano La Manna; Miguel Fribourg; Jeremy Leventhal; Stefano Da Sacco; Laura Perin; Peter S Heeger; Paolo Cravedi Journal: J Exp Med Date: 2020-09-07 Impact factor: 17.579