TXNIP Exacerbates the Senescence and Aging-Related Dysfunction of beta Cells by Inducing Cell Cycle Arrest Through p38-p16/p21-CDK-Rb Pathway

作者全名："Li, Yang; Deng, Wenzhen; Wu, Jinlin; He, Qirui; Yang, Gangyi; Luo, Xie; Jia, Yanjun; Duan, Yaqian; Zhou, Liping; Liu, Dongfang"

作者地址："[Li, Yang; Deng, Wenzhen; Wu, Jinlin; He, Qirui; Yang, Gangyi; Luo, Xie; Jia, Yanjun; Duan, Yaqian; Liu, Dongfang] Chongqing Med Univ, Affiliated Hosp 2, Dept Endocrinol, Chongqing 400010, Peoples R China; [Deng, Wenzhen] Qianjiang Cent Hosp Chongqing, Dept Endocrinol, Chongqing, Peoples R China; [Wu, Jinlin; Zhou, Liping] Chongqing Tradit Chinese Med Hosp, Dept Endocrinol, Chongqing, Peoples R China"

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

来源：ANTIOXIDANTS & REDOX SIGNALING

ESI学科分类：BIOLOGY & BIOCHEMISTRY

WOS号：WOS:000953034700002

JCR分区：Q1

影响因子：5.9

年份：2023

卷号：38

期号：7月9日

开始页：480

结束页：495

文献类型：Article

关键词：TXNIP; beta cell; cellular senescence; cell cycle; p38MAPK

摘要："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."

基金机构："National Natural Science Foundation of China [81370467, 81800771, 82100824]; Chinese Postdoctoral Science Foundation [2021M700633]; Natural Science Foundation Project of CQ [cstc2019jxjl130028, cstc2021jcyj-msxmX0074]; China Endocrinology and Metabolism Young Scientific Talent Research Project [2021-N-03]"

基金资助正文："The study was supported by the grant from the National Natural Science Foundation of China (81370467, 81800771, 82100824), Chinese Postdoctoral Science Foundation (2021M700633), the Natural Science Foundation Project of CQ (cstc2019jxjl130028; cstc2021jcyj-msxmX0074), and the China Endocrinology and Metabolism Young Scientific Talent Research Project (2021-N-03)."