Role and mechanism of TXNIP in ageing-related renal fibrosis. (June 2021)

• Record Type: Journal Article
• Authors: He, Qirui; Li, Yang; Zhang, Weiwei; Chen, Jie; Deng, Wenzhen; Liu, Qicong; Liu, Yongjian; Liu, Dongfang
• Is Part Of: Mechanisms of ageing and development. Volume 196(2021)
• Publication Date: 2021-06
• Subjects: TXNIP -- Kidney ageing -- Renal fibrosis -- STAT3 signalling pathway; Aging -- Periodicals; Developmental biology -- Periodicals; Aging -- Periodicals; Developmental Biology -- Periodicals; Vieillissement -- Périodiques; Biologie du développement -- Périodiques; Aging; Developmental biology; Periodicals; 612.67
• DOI: 10.1016/j.mad.2021.111475
• Languages: English
• ISSNs: 0047-6374

Abstract

Highlights: The expression of TXNIP gradually increases with ageing in kidneys. TXNIP protein plays a crucial role in the ageing related renal fibrosis. TXNIP exacerbates the renal tubular fibrosis via a STAT3-TGF-β1/Smad3 pathway. Abstract: 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.