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Updated: Aug 19, 2025

Identification of the Source of Secreted Proteins in the Kidney by Brefeldin A Injection
Published on: November 10, 2021
TWIK-related acid-sensitive K+ channel 2 promotes renal fibrosis by inducing cell-cycle arrest
Jian Zhang1,2, Jing Chen2,3,4,5,6, Yufei Lu2,3,4,5,6
1Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China.
Abstract:
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.
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