Role and mechanism of TXNIP in ageing-related renal fibrosis

作者全名："He, Qirui; Li, Yang; Zhang, Weiwei; Chen, Jie; Deng, Wenzhen; Liu, Qicong; Liu, Yongjian; Liu, Dongfang"

作者地址："[He, Qirui; Li, Yang; Zhang, Weiwei; Chen, Jie; Deng, Wenzhen; Liu, Qicong; Liu, Yongjian; Liu, Dongfang] Chongqing Med Univ, Affiliated Hosp 2, Dept Endocrinol, Chongqing 400010, Peoples R China; [Deng, Wenzhen] Qianjiang Cent Hosp Chongqing, Dept Endocrinol, Chongqing 409000, Peoples R China; [Liu, Dongfang] Chongqing Clin Res Ctr Geriatr & Gerontol, Chongqing 409000, Peoples R China"

通信作者："Liu, DF (corresponding author), Chongqing Med Univ, Affiliated Hosp 2, Dept Endocrinol, Chongqing 400010, Peoples R China."

来源：MECHANISMS OF AGEING AND DEVELOPMENT

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:000653421900009

JCR分区：Q2

影响因子：5.3

年份：2021

卷号：196

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：TXNIP; Kidney ageing; Renal fibrosis; STAT3 signalling pathway

摘要："Kidney ageing, which is always accompanied by renal fibrosis, drives the progression of renal fibrosis. Thioredoxin-interacting protein (TXNIP) is an endogenous suppressor of the reactive oxygen species-scavenging protein thioredoxin, which has been implicated in the ageing of some organs and is involved in renal fibrosis. However, the expression of TXNIP in ageing kidneys has not been examined, and the relationship between TXNIP and ageing-related renal fibrosis is unclear. We found that TXNIP expression was upregulated in aged mouse kidneys, and this upregulation was accompanied by ageing-related renal fibrosis phenotypes. We demonstrated that the ageing biomarkers were downregulated in TXNIP-knockout mice, and these effects resulted in the alleviation of renal fibrosis and impairments in kidney function. TXNIP overexpression in tubular cells upregulated senescence markers, promoted a profibrotic response and activated STAT3 signalling, and these parameters were inhibited by the silencing of TXNIP. Similarly, the TXNIP-mediated profibrotic response was significantly suppressed by a STAT3 inhibitor. By coimmunoprecipitation, we verified that TXNIP directly bound to STAT3, which suggested that TXNIP exacerbates renal tubular epithelial fibrosis by activating the STAT3 pathway. In summary, TXNIP plays an important role in age-related renal fibrosis and might be a therapeutic target for preventing ageing-associated renal fibrosis."

基金机构：National Natural Science Foundation of China [81370467]; Natural Science Foundation Project of Chongqing [cstc2017shmsA130069]; Medical Scientific Research Project of the Chongqing Health Planning Committee [2016ZDXM011]

基金资助正文："We thank the National Natural Science Foundation of China (81370467), the Natural Science Foundation Project of Chongqing (cstc2017shmsA130069), and the Medical Scientific Research Project of the Chongqing Health Planning Committee (2016ZDXM011) for supporting this work."