IQGAP1 mediates podocyte injury in diabetic kidney disease by regulating nephrin endocytosis
作者
Liu, YP;Su, H;Ma, CQ;Ji, D;Zheng, XL;Wang, P;Zheng, SX;Wang, L;Wang, ZS;Xu, DM
作者单位
[Liu, Yipeng; Su, Hong; Wang, Ping; Wang, Li; Wang, Zunsong; Xu, Dongmei] Shandong Univ, Shandong Prov Qianfoshan Hosp, Dept Nephrol, 16766 Jingshi Rd, Jinan 250014, Shandong, Peoples R China.;-;[Su, Hong] Shandong Univ, Shandong Prov Hosp, Dept Nephrol, Jinan 250021, Shandong, Peoples R China.;-;[Ma, Chaoqun; Zheng, Xiaoli] Shandong Univ, Shandong Prov Hosp, Dept Emergency, Jinan 250021, Shandong, Peoples R China.;-;[Ji, Dong] Huimin Cty Peoples Hosp, Dept Dialysis, Binzhou 251700, Peoples R China.;-;[Zheng, Shixiang] Fujian Med Univ, Union Hosp, Div Crit Care Med, Fuzhou 350001, Fujian, Peoples R China.
摘要
Diabetic kidney disease (DKD) is a complication associated with diabetes and is a major public health problem in modern society. Podocyte injury is the central target of the development of DKD, and the loss or dysregulation of nephrin, a key structural and signalling molecule located in the podocyte slit diaphragm (SD), initiates potentially catastrophic downstream events within podocytes. IQGAP1, a scaffold protein containing multiple-binding domains that regulates endocytosis, can interact with nephrin in podocytes. It is hypothesized that IQGAP1 contributes to nephrin endocytosis and may participate in the pathogenesis of DKD. The dramatically increased histo-nephrin granularity score in DKD glomeruli showed a significant positive correlation with increased IQGAP1-nephrin interaction without changes in the total protein content of nephrin and IQGAP1. In cultured human podocytes, hyperglycaemia induced the intracellular translocation of IQGAP1 from the cytosol to the vicinity of the cytomembrane, reinforced the IQGAP1-nephrin interaction, and augmented nephrin endocytosis. Moreover, impaired podocyte function, such as migration, extensibility and permeability, were further aggravated by wild-type IQGAP1 plasmid transfection, and these effects were partially restored by siRNA-mediated IQGAP1 downregulation. Collectively, these findings show that IQGAP1, an intracellular partner of nephrin, is involved in nephrin endocytosis and the functional regulation of podocytes in DKD.
关键词
PROTEINS; TRAFFICKING; BIOLOGY; BINDING; DOMAIN
基本信息
