High glucose reduces the expression of podocin in cultured human podocytes by stimulating TRPC6.

High glucose reduces the expression of podocin in cultured human podocytes by stimulating TRPC6. Am J Physiol Renal Physiol. 2019 Sep 30;: Authors: Lu XY, Liu BC, Cao YZ, Song C, Su H, Chen G, Klein JD, Zhang HX, Wang L, Ma HP Abstract The transient receptor potential canonical 6 (TRPC6) channel and podocin are co-localized in the glomerular slit diaphragm as an important complex to maintain podocyte function. Gain of TRPC6 function and loss of podocin function induce podocyte injury. We have previously shown that high glucose induces apoptosis of podocytes by activating TRPC6; however, whether the activated TRPC6 can alter podocin expression remains unknown. Western blot, confocal microscopy, and scanning ion conductance microscopy were used to examine both the expression levels of TRPC6, podocin, and nephrin and the morphological change of podocytes in response to high glucose. High glucose increased the expression of TRPC6, but reduced the expression of podocin and nephrin, both in cultured human podocytes and in type 1 diabetic rat kidney. The decreased podocin was diminished in TRPC6 knockdown podocytes. High glucose elevated intracellular calcium in control podocytes, but not in TRPC6 knockdown podocytes. High glucose also elevated the expression of a tight junction protein, zonula occludens-1 (ZO-1) and induced the redistribution of ZO-1 and the loss of podocyte processes. These data together suggest that high glucose reduces ...
Source: American Journal of Physiology. Renal Physiology - Category: Physiology Authors: Tags: Am J Physiol Renal Physiol Source Type: research