TWIK-related acid-sensitive K+ channel 2 promotes renal fibrosis by inducing cell-cycle arrest

TWIK-related acid-sensitive K+ channel-2 (TASK-2, encoded by Kcnk5) is essential in cell biological processes, by regulating transmembrane K+ balance. In the present study, we aimed to clarify the role of TASK-2 in renal fibrosis and explore the underlying mechanism. We found that TASK-2 level was elevated in the renal tubular UUO- and UIR-induced renal fibrosis as well as in patients with renal tubulointerstitial fibrosis. Knockout of Kcnk5 or inhibition of TASK-2 in renal tubules attenuated G2/M cell-cycle arrest and alleviated renal fibrosis. Mechanistically, demethylase fat mass and obesity-associated protein (FTO) reduced N6-adenosine methylation (m6A) of Kcnk5 mRNA following renal fibrosis. FTO deficiency attenuated the upregulation of TASK-2 and renal fibrosis. The results demonstrated the crucial role of TASK-2 in renal fibrosis, which is conducive to a better understanding of the pathogenesis of renal fibrosis. TASK-2 may be a potential treatment strategy to alleviate the development of renal fibrosis. [Display omitted] •TWIK-related acid-sensitive K+ channel 2 (TASK-2) is up-regulated in renal fibrosis•Inhibition of TASK-2 alleviates renal fibrosis via reducing G2/M arrest•Activation of TASK-2 reduced intracellular K+ and leads to fibrogenesis•TASK-2 overexpression in renal fibrosis is mediated by FTO through m6A modification Nephrology; Molecular biology; Cell biology