IQGAP1 mediates podocyte injury in diabetic kidney disease by regulating nephrin endocytosis.

Authors:
Hong Su
Hong Su
School of Public Health
New Haven | United States
Chaoqun Ma
Chaoqun Ma
Provincial Hospital Affiliated to Shandong University (East District) Jinan 250014
Dong Ji
Dong Ji
Institute of Infectious Diseases
China
Xiaoli Zheng
Xiaoli Zheng
Zhengzhou University
China
Ping Wang
Ping Wang
Albert Einstein College of Medicine
United States
Shixiang Zheng
Shixiang Zheng
Renmin Hospital of Wuhan University
MRs Li Wang, RN
MRs Li Wang, RN
shepherd university
RN
RN
walnut , CA | United States

Cell Signal 2019 Jul 9;59:13-23. Epub 2019 Mar 9.

Department of Nephrology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan 250014, China. Electronic address:

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 protein-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.

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http://dx.doi.org/10.1016/j.cellsig.2019.03.009DOI Listing
July 2019
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