iScience (Dec 2022)
TWIK-related acid-sensitive K+ channel 2 promotes renal fibrosis by inducing cell-cycle arrest
- Jian Zhang,
- Jing Chen,
- Yufei Lu,
- Yan Yang,
- Weize Chen,
- Bo Shen,
- Jiachang Hu,
- Ping Jia,
- Sujuan Xu,
- Yiqin Shi,
- Yichun Ning,
- Jialin Wang,
- Yi Fang,
- Shuan Zhao,
- Yang Li,
- Yan Dai,
- Xiaoyan Zhang,
- Meng Xiang,
- Yang Tian,
- Zhichao Liu,
- Nana Song,
- Xiaoqiang Ding
Affiliations
- Jian Zhang
- Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China; Department of Nephrology, Zhongshan Hospital, Fudan University, Shanghai 200032, China
- Jing Chen
- Department of Nephrology, Zhongshan Hospital, Fudan University, Shanghai 200032, China; Shanghai Medical Center of Kidney, Shanghai 200032, China; Shanghai Institute of Kidney and Dialysis, Shanghai 200032, China; Shanghai Key Laboratory of Kidney and Blood Purification, Shanghai 200032, China; Hemodialysis Quality Control Center of Shanghai, Shanghai 200032, China
- Yufei Lu
- Department of Nephrology, Zhongshan Hospital, Fudan University, Shanghai 200032, China; Shanghai Medical Center of Kidney, Shanghai 200032, China; Shanghai Institute of Kidney and Dialysis, Shanghai 200032, China; Shanghai Key Laboratory of Kidney and Blood Purification, Shanghai 200032, China; Hemodialysis Quality Control Center of Shanghai, Shanghai 200032, China
- Yan Yang
- Department of Nephrology, Zhongshan Hospital, Fudan University, Shanghai 200032, China; Shanghai Medical Center of Kidney, Shanghai 200032, China; Shanghai Institute of Kidney and Dialysis, Shanghai 200032, China; Shanghai Key Laboratory of Kidney and Blood Purification, Shanghai 200032, China; Hemodialysis Quality Control Center of Shanghai, Shanghai 200032, China
- Weize Chen
- Department of Nephrology, Zhongshan Hospital, Fudan University, Shanghai 200032, China; Shanghai Medical Center of Kidney, Shanghai 200032, China; Shanghai Institute of Kidney and Dialysis, Shanghai 200032, China; Shanghai Key Laboratory of Kidney and Blood Purification, Shanghai 200032, China; Hemodialysis Quality Control Center of Shanghai, Shanghai 200032, China
- Bo Shen
- Department of Nephrology, Zhongshan Hospital, Fudan University, Shanghai 200032, China; Shanghai Medical Center of Kidney, Shanghai 200032, China; Shanghai Institute of Kidney and Dialysis, Shanghai 200032, China; Shanghai Key Laboratory of Kidney and Blood Purification, Shanghai 200032, China; Hemodialysis Quality Control Center of Shanghai, Shanghai 200032, China
- Jiachang Hu
- Department of Nephrology, Zhongshan Hospital, Fudan University, Shanghai 200032, China; Shanghai Medical Center of Kidney, Shanghai 200032, China; Shanghai Institute of Kidney and Dialysis, Shanghai 200032, China; Shanghai Key Laboratory of Kidney and Blood Purification, Shanghai 200032, China; Hemodialysis Quality Control Center of Shanghai, Shanghai 200032, China
- Ping Jia
- Department of Nephrology, Zhongshan Hospital, Fudan University, Shanghai 200032, China; Shanghai Medical Center of Kidney, Shanghai 200032, China; Shanghai Institute of Kidney and Dialysis, Shanghai 200032, China; Shanghai Key Laboratory of Kidney and Blood Purification, Shanghai 200032, China; Hemodialysis Quality Control Center of Shanghai, Shanghai 200032, China
- Sujuan Xu
- Department of Nephrology, Zhongshan Hospital, Fudan University, Shanghai 200032, China; Shanghai Medical Center of Kidney, Shanghai 200032, China; Shanghai Institute of Kidney and Dialysis, Shanghai 200032, China; Shanghai Key Laboratory of Kidney and Blood Purification, Shanghai 200032, China; Hemodialysis Quality Control Center of Shanghai, Shanghai 200032, China
- Yiqin Shi
- Department of Nephrology, Zhongshan Hospital, Fudan University, Shanghai 200032, China; Shanghai Medical Center of Kidney, Shanghai 200032, China; Shanghai Institute of Kidney and Dialysis, Shanghai 200032, China; Shanghai Key Laboratory of Kidney and Blood Purification, Shanghai 200032, China; Hemodialysis Quality Control Center of Shanghai, Shanghai 200032, China
- Yichun Ning
- Department of Nephrology, Zhongshan Hospital, Fudan University, Shanghai 200032, China; Shanghai Medical Center of Kidney, Shanghai 200032, China; Shanghai Institute of Kidney and Dialysis, Shanghai 200032, China; Shanghai Key Laboratory of Kidney and Blood Purification, Shanghai 200032, China; Hemodialysis Quality Control Center of Shanghai, Shanghai 200032, China
- Jialin Wang
- Department of Nephrology, Zhongshan Hospital, Fudan University, Shanghai 200032, China; Shanghai Medical Center of Kidney, Shanghai 200032, China; Shanghai Institute of Kidney and Dialysis, Shanghai 200032, China; Shanghai Key Laboratory of Kidney and Blood Purification, Shanghai 200032, China; Hemodialysis Quality Control Center of Shanghai, Shanghai 200032, China
- Yi Fang
- Department of Nephrology, Zhongshan Hospital, Fudan University, Shanghai 200032, China; Shanghai Medical Center of Kidney, Shanghai 200032, China; Shanghai Institute of Kidney and Dialysis, Shanghai 200032, China; Shanghai Key Laboratory of Kidney and Blood Purification, Shanghai 200032, China; Hemodialysis Quality Control Center of Shanghai, Shanghai 200032, China
- Shuan Zhao
- Department of Nephrology, Zhongshan Hospital, Fudan University, Shanghai 200032, China; Shanghai Medical Center of Kidney, Shanghai 200032, China; Shanghai Institute of Kidney and Dialysis, Shanghai 200032, China; Shanghai Key Laboratory of Kidney and Blood Purification, Shanghai 200032, China; Hemodialysis Quality Control Center of Shanghai, Shanghai 200032, China
- Yang Li
- Department of Nephrology, Zhongshan Hospital, Fudan University, Shanghai 200032, China; Shanghai Medical Center of Kidney, Shanghai 200032, China; Shanghai Institute of Kidney and Dialysis, Shanghai 200032, China; Shanghai Key Laboratory of Kidney and Blood Purification, Shanghai 200032, China; Hemodialysis Quality Control Center of Shanghai, Shanghai 200032, China
- Yan Dai
- Department of Nephrology, Zhongshan Hospital, Fudan University, Shanghai 200032, China; Shanghai Medical Center of Kidney, Shanghai 200032, China; Shanghai Institute of Kidney and Dialysis, Shanghai 200032, China; Shanghai Key Laboratory of Kidney and Blood Purification, Shanghai 200032, China; Hemodialysis Quality Control Center of Shanghai, Shanghai 200032, China
- Xiaoyan Zhang
- Department of Nephrology, Zhongshan Hospital, Fudan University, Shanghai 200032, China; Shanghai Medical Center of Kidney, Shanghai 200032, China; Shanghai Institute of Kidney and Dialysis, Shanghai 200032, China; Shanghai Key Laboratory of Kidney and Blood Purification, Shanghai 200032, China; Hemodialysis Quality Control Center of Shanghai, Shanghai 200032, China
- Meng Xiang
- Department of Physiology and Pathophysiology, Fudan University, Shanghai 200032, China
- Yang Tian
- Department of Chemistry, East China Normal University, Shanghai 200241, China
- Zhichao Liu
- Department of Chemistry, East China Normal University, Shanghai 200241, China
- Nana Song
- Department of Nephrology, Zhongshan Hospital, Fudan University, Shanghai 200032, China; Shanghai Medical Center of Kidney, Shanghai 200032, China; Shanghai Institute of Kidney and Dialysis, Shanghai 200032, China; Shanghai Key Laboratory of Kidney and Blood Purification, Shanghai 200032, China; Hemodialysis Quality Control Center of Shanghai, Shanghai 200032, China; Fudan Zhangjiang Institute, Shanghai 201203, China; Corresponding author
- Xiaoqiang Ding
- Department of Nephrology, Zhongshan Hospital, Fudan University, Shanghai 200032, China; Shanghai Medical Center of Kidney, Shanghai 200032, China; Shanghai Institute of Kidney and Dialysis, Shanghai 200032, China; Shanghai Key Laboratory of Kidney and Blood Purification, Shanghai 200032, China; Hemodialysis Quality Control Center of Shanghai, Shanghai 200032, China; Corresponding author
- Journal volume & issue
-
Vol. 25,
no. 12
p. 105620
Abstract
Summary: 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.
