Gap junctions amplify TRPV4 activation-initiated cell injury via modification of intracellular Ca²⁺ and Ca²⁺-dependent regulation of TXNIP.

ABSTRACT: The elevated intracellular Ca²⁺ and oxidative stress are well-reported mechanisms behind renal tubular epithelial injury initiated by various insults. Given that TRPV4 and connexin43 (Cx43) channels are activated by a wide range of stimuli and regulate both intracellular Ca²⁺ and redox status, we speculated an involvement of these channels in renal tubular cell injury. Here, we tested this possibility and explored the potential underlying mechanisms. Our results demonstrated that exposure of renal tubular epithelial cells to aminoglycoside G418 led to cell death, which was attenuated by both TRPV4 and gap junction (Gj) inhibitor. Activation of TRPV4 caused cell damage, which was associated with an early increase in Cx43 expression and function. Inhibition of Cx43 with

SUBMITTER: Zhang X 

PROVIDER: S-EPMC7515575 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature