The role of TRPC6 in oxidative stress-induced podocyte ischemic injury.

Abstract

Increasing evidence suggests that ischemia and hypoxia serve important functions in the development of renal diseases. However, the underlying mechanism of ischemic injury has not been fully understood. In this study, we found that renal ischemia-reperfusion injury induced podocyte effacement and the upregulation of TRPC6 mRNA and protein expression. In in vitro experiments, oxygen glucose deprivation (OGD) treatment enhanced the expression of TRPC6 and TRPC6-dependent Ca(2+) influx. TRPC6 knockdown by siRNA interference attenuated the OGD-induced [Ca(2+)]i and actin assembly. OGD treatment also increased ROS production. Furthermore, inhibition of ROS activity by N-acetyl-l-cysteine (NAC) eliminated the OGD-induced increase in TRPC6 expression and Ca(2+) influx. H2O2 treatment, which results in oxidative stress, also increased TRPC6 expression and Ca(2+) influx. We conclude that TRPC6 upregulation is involved in Ca(2+) signaling and actin reorganization in podocytes after OGD. These findings provide new insight into the mechanisms underlying the cellular response of podocytes to ischemic injury.