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

doi:10.1016/j.isci.2022.105620

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^*

^*Corresponding author for this work

School of Chemistry and Molecular Engineering

Fudan University
Shanghai Medical Center of Kidney
Shanghai Institute of Kidney and Dialysis
Shanghai Key Laboratory of Kidney and Blood Purification
Hemodialysis Quality Control Center of Shanghai
Fudan Zhangjiang Institute

Research output: Contribution to journal › Article › peer-review

13 Scopus citations

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.

Original language	English
Article number	105620
Journal	iScience
Volume	25
Issue number	12
DOIs	https://doi.org/10.1016/j.isci.2022.105620
State	Published - 22 Dec 2022

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Nephrology
cell biology
molecular biology

Access to Document

10.1016/j.isci.2022.105620

Cite this

Zhang, J., Chen, J., Lu, Y., Yang, Y., Chen, W., Shen, B., Hu, J., Jia, P., Xu, S., Shi, Y., Ning, Y., Wang, J., Fang, Y., Zhao, S., Li, Y., Dai, Y., Zhang, X., Xiang, M., Tian, Y., ... Ding, X. (2022). TWIK-related acid-sensitive K⁺ channel 2 promotes renal fibrosis by inducing cell-cycle arrest. iScience, 25(12), Article 105620. https://doi.org/10.1016/j.isci.2022.105620

@article{97cfd775627e497e9935e2faa7952a9e,

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

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.",

keywords = "Nephrology, cell biology, molecular biology",

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

note = "Publisher Copyright: {\textcopyright} 2022 The Author(s)",

year = "2022",

month = dec,

day = "22",

doi = "10.1016/j.isci.2022.105620",

language = "英语",

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Zhang, J, Chen, J, Lu, Y, Yang, Y, Chen, W, Shen, B, Hu, J, Jia, P, Xu, S, Shi, Y, Ning, Y, Wang, J, Fang, Y, Zhao, S, Li, Y, Dai, Y, Zhang, X, Xiang, M, Tian, Y , Liu, Z, Song, N & Ding, X 2022, 'TWIK-related acid-sensitive K⁺ channel 2 promotes renal fibrosis by inducing cell-cycle arrest', iScience, vol. 25, no. 12, 105620. https://doi.org/10.1016/j.isci.2022.105620

TY - JOUR

T1 - TWIK-related acid-sensitive K+ channel 2 promotes renal fibrosis by inducing cell-cycle arrest

AU - Zhang, Jian

AU - Chen, Jing

AU - Lu, Yufei

AU - Yang, Yan

AU - Chen, Weize

AU - Shen, Bo

AU - Hu, Jiachang

AU - Jia, Ping

AU - Xu, Sujuan

AU - Shi, Yiqin

AU - Ning, Yichun

AU - Wang, Jialin

AU - Fang, Yi

AU - Zhao, Shuan

AU - Li, Yang

AU - Dai, Yan

AU - Zhang, Xiaoyan

AU - Xiang, Meng

AU - Tian, Yang

AU - Liu, Zhichao

AU - Song, Nana

AU - Ding, Xiaoqiang

PY - 2022/12/22

Y1 - 2022/12/22

N2 - 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.

AB - 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.

KW - Nephrology

KW - cell biology

KW - molecular biology

UR - https://www.scopus.com/pages/publications/85145703440

U2 - 10.1016/j.isci.2022.105620

DO - 10.1016/j.isci.2022.105620

M3 - 文章

AN - SCOPUS:85145703440

SN - 2589-0042

VL - 25

JO - iScience

JF - iScience

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M1 - 105620

ER -