期刊
ANTIOXIDANTS & REDOX SIGNALING
卷 38, 期 7-9, 页码 480-495出版社
MARY ANN LIEBERT, INC
DOI: 10.1089/ars.2021.0224
关键词
TXNIP; beta cell; cellular senescence; cell cycle; p38MAPK
This study investigated the effects and mechanisms of TXNIP on the senescence and aging- and diet-related dysfunction of beta cells. The results showed that TXNIP expression was age-related in human beta cells and serum samples. TXNIP induced cell cycle arrest through the p38-p16/p21-CDK-Rb pathway, accelerating beta cell senescence and age-related dysfunction.
Aims: Thioredoxin-interacting protein (TXNIP) is a crucial molecular promoter of oxidative stress and has been identified to be associated with cellular senescence. It is an important mediator of beta cell insulin secretion and has effects on beta cell mass. However, its role in beta cell senescence is unclear. The present study was designed to investigate the effects and mechanisms of TXNIP on the senescence and aging- and diet-related dysfunction of beta cells.Methods: Human pancreatic paraffin tissues and serum samples from different ages were collected to detect TXNIP expression. TXNIP-/- and C57BL/6J mice were fed either a normal chow diet (NCD) or a high-fat diet (HFD) until 5, 11, 14, or 20 months. The recapitulation experiment was conducted with TXNIP protein injection. MIN6 cells were transfected with LV-TXNIP and LV-siTXNIP. The biochemical indexes, ageing-related markers, cell cycle proteins, and pathways were examined both in vivo and in vitro.Results: TXNIP expression showed an age-related increase in beta cells and serum samples from humans. TXNIP significantly impaired glucose metabolism and insulin secretion in an age-dependent manner. TXNIP aggravated age-related and obesity-induced structural failure, oxidative stress, decreased proliferation, increased apoptosis in beta cells, and induced the cell cycle arrest. TXNIP interacted with p38 mitogen-activated protein kinase (p38MAPK) and modulated the p16/p21-CDK-Rb axis to accelerate beta cell senescence.Innovation and Conclusions: The present study demonstrated that TXNIP may exacerbate pancreatic beta cell senescence and age-related dysfunction by inducing cell cycle arrest through the p38-p16/p21-CDK-Rb pathway, in natural and pathological states. Antioxid. Redox Signal. 38, 480-495.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据