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

作者：Zhang, Jian; Chen, Jing; Lu, Yufei; Yang, Yan; Chen, Weize; Shen, Bo; Hu, Jiachang; Jia, Ping; Xu, Sujuan; Shi, Yiqin; Ning, Yichun; Wang, Jialin; Fang, Yi; Zhao, Shuan; Li, Yang; Dai, Yan; Zhang, Xiaoyan; Xiang, Meng; Tian, Yang; Liu, Zhichao; Song, Nana; Ding, Xiaoqiang

来源：iScience, 2022, 25(12): 105620.

DOI：10.1016/j.isci.2022.105620

• CHRONIC KIDNEY-DISEASE
• POTASSIUM CHANNELS
• DIETARY POTASSIUM
• RISK
• PROLIFERATION
• HYPERTENSION
• NEPHROPATHY
• TRANSLATION
• TRANSITION
• INJURY

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.

• 单位
  复旦大学