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.
Highlights
Transient receptor potential canonical channel 6 (TRPC6) is a nonselective Ca2+ channel protein
Heparan sulfate proteoglycan syndecan-4 (Sdc4) can interact with TRPC6, promotes its expression, and transports it to the cell surface in podocytes [88], resulting in reduced activation of Rho A and increased activation of Rac1, accompanied by increased generation of reactive oxygen species (ROS) and total β3-integrin [89]. All these results suggest that TRPC6 plays a more direct and critical role in podocyte actin cytoskeleton rearrangement
How do the TRPC6/calpain change in the diabetic kidney disease (DKD) podocyte injury? Our results showed that there was a significantly loss of the podocyte talin1 on the mRNA level and protein level in a DKD mouse model, which was strongly positively correlated to the severity of proteinuria and podocyte actin cytoskeleton rearrangement
Summary
Transient receptor potential canonical channel 6 (TRPC6) is a nonselective Ca2+ channel protein. It is known that TRPC6 can participate in podocyte injury by regulating the rearrangement of actin cytoskeleton and eventually leads to proteinuria. The changes of podocyte number and/or structure of foot process have been demonstrated to be the main cause leading to glomerular proteinuria [2]. Numerous studies on podocyte have shown that actin cytoskeleton rearrangement induced by multiple pathogenic factors is the key alteration leading to podocyte injury [3, 4], and its mechanisms have remained elusive. More and more studies have shown that aberrant changes of TRPC6 in podocyte play an important role in the proteinuria development and DKD progression. The mechanism may involve the rearrangement of podocyte actin cytoskeleton. The precise mechanism has not yet been determined, and further research is urgently needed
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
