Role of Transient Receptor Potential Canonical Channel 6 (TRPC6) in Diabetic Kidney Disease by Regulating Podocyte Actin Cytoskeleton Rearrangement

Abstract

Podocyte injury is an important pathogenesis step causing proteinuric kidney diseases such as diabetic kidney disease (DKD). Actin cytoskeleton rearrangement in podocyte induced by multiple pathogenic factors is believed to be the key process resulting in glomerular injury. Many studies have recently shown that transient receptor potential canonical channel 6 (TRPC6) in podocyte plays a critical role in the development and progression of proteinuric kidney disease by regulating its actin cytoskeleton rearrangement. This review is aimed at summarizing the role of TRPC6 on DKD by regulating the podocyte actin cytoskeleton rearrangement, thereby help further broaden our views and understanding on the mechanism of DKD and provide a theoretic basis for exploring new therapeutic targets for DKD patients.

Figure 1

TRPC6 is involved in the rearrangement of podocyte actin cytoskeleton. In DKD, various stimulating factors lead to high expression of TRPC6 and a large amount of Ca²⁺ influx, causing podocyte hypertrophy and foot process effacement. By binding Rho GTPase family proteins to ROCK, F-actin becomes disordered, shortened, and branched (a), or talins are abnormally cleaved by activation of calpain (b), causes the destruction of podocyte focal adhesion complex structure, increased motility, and ultimately leads to foot processes effacement, detachment of podocytes, and proteinuria. Abbreviations: FP: foot process; TRPC6: transient receptor potential canonical channel 6; Rho GTPase: Rho guanosine triphosphatase (Rho A, Rac1, and Cdc42); ROCK: Rho-associated coiled-coil protein kinase; GBM: glomerular basement membrane; ROS: reactive oxygen species; Ang II: angiotensin II.