Aug 11 2021

Target Molecules for Developing Novel Therapies for Proteinuria Newly Identified

A research group of Professor KAWACHI Hiroshi and Associate Professor FUKUSUMI Yoshiyasu of the Department of Cell Biology in the Kidney Research Center, Niigata University Graduate School of Medical and Dental Sciences, elucidated the molecular linking structure for maintaining the barrier function of the renal glomerular epithelial cell’s slit diaphragm, which is responsible for proteinuria, which proteins in the blood have leaked into the urine, and clarified the mechanism by which the linking structure collapses and proteinuria develops. Many unknown areas about the proteinuria onset mechanism exist; no effective therapeutic drugs have yet been developed. This research, published in the American Journal of Pathology on July 1, 2021, is expected to contribute to developing new therapy for proteinuria.

Research Results

• NHERF2, a cell membrane lining molecule, was determined to play an important role in maintaining the barrier function of the renal glomerular epithelial cell’s slit diaphragm, preventing proteinuria.
• NHERF2 was demonstrated to be a molecule connecting nephrin and ephrin-B1, which are cell membrane molecules of the slit diaphragm, with ezrin, which is a cytoskeleton-related molecule, and is important for stabilizing the slit diaphragm structure and maintaining its function. When the slit diaphragm is stimulated, NHERF2 is dephosphorylated and the connecting structure between the slit diaphragm and the cytoskeleton are disrupted, leading to proteinuria.
• A novel therapeutic method for proteinuria that suppresses dephosphorylation of NHERF2 is expected to be developed.

Publication Details

Journal: American Journal of Pathology
Title: Nephrin–Ephrin-B1–Na⁺/H⁺ Exchanger Regulatory Factor 2–Ezrin–Actin Axis Is Critical in Podocyte Injury
Authors: Yoshiyasu Fukusumi, Hidenori Yasuda, Ying Zhang, Hiroshi Kawachi
DOI: 10.1016/j.ajpath.2021.04.004