RNA-binding protein HuR suppresses senescence through Atg7 mediated autophagy activation in diabetic intervertebral disc degeneration.
RNA-binding protein HuR suppresses senescence through Atg7 mediated autophagy activation in diabetic intervertebral disc degeneration.
复制标题
RNA-结合蛋白 HuR 通过 Atg7 介导的糖尿病椎间盘退变中的自噬激活来抑制衰老
DOI：
10.1111/cpr.12975
复制
发表时间：
2021-03
影响因子：
8.5
通讯作者：
Wang X
中科院分区：
文献类型：
--
作者：
Shao Z;Ni L;Hu S;Xu T;Meftah Z;Yu Z;Tian N;Wu Y;Sun L;Wu A;Pan Z;Chen L;Gao W;Zhou Y;Zhang X;Wang X
糖尿病是椎间盘退变（IVDD）的危险因素。研究表明，糖尿病可能通过转录调控影响IVDD；然而，是否转录后调控参与糖尿病IVDD （DB - IVDD）仍是未知的。本研究旨在阐明HuR（一种RNA结合蛋白）在DB - IVDD发育中的作用及其机制。HuR在糖尿病IVDD患者髓核（NP）组织和高糖处理的NP细胞中的表达进行了评估。观察HuR过表达和下调的NP细胞的衰老和自噬情况。筛选受HuR调控的mrna，应用免疫沉淀法确认HuR对靶mrna的调控作用。结果表明，在糖尿病NP组织和高糖处理的NP细胞中，HuR的表达降低。在高糖处理的NP细胞中，HuR的下调可能导致衰老增加，而自噬激活则会减缓HuR缺乏的NP细胞的衰老。机制研究表明，HuR通过与富AU元素结合促进Atg7 mRNA的稳定性。此外，Atg7的过表达，而不是HuR的过表达，可能会改善大鼠体内的DB - IVDD。综上所述，HuR可能通过稳定糖尿病NP细胞的Atg7激活自噬来抑制衰老；而Atg7，而不是HuR，可能作为DB - IVDD的潜在治疗靶点。在高糖处理下，HuR的表达降低，导致自噬失活和衰老加剧。机制研究表明，HuR通过结合Atg7富AU元素调节Atg7 mRNA的稳定性，从而调控Atg7的表达
Diabetes is a risk factor for intervertebral disc degeneration (IVDD). Studies have demonstrated that diabetes may affect IVDD through transcriptional regulation; however, whether post‐transcriptional regulation is involved in diabetic IVDD (DB‐IVDD) is still unknown. This study was performed to illustrate the role of HuR, an RNA‐binding protein, in DB‐IVDD development and its mechanism. The expression of HuR was evaluated in nucleus pulposus (NP) tissues from diabetic IVDD patients and in high glucose‐treated NP cells. Senescence and autophagy were assessed in HuR over‐expressing and downregulation NP cells. The mRNAs that were regulated by HuR were screened, and immunoprecipitation was applied to confirm the regulation of HuR on targeted mRNAs. The results showed that the expression of HuR was decreased in diabetic NP tissues and high glucose‐treated NP cells. Downregulation of HuR may lead to increased senescence in high glucose‐treated NP cells, while autophagy activation attenuates senescence in HuR deficient NP cells. Mechanistic study showed that HuR prompted Atg7 mRNA stability via binding to the AU‐rich elements. Furthermore, overexpression of Atg7, but not HuR, may ameliorate DB‐IVDD in rats in vivo. In conclusion, HuR may suppress senescence through autophagy activation via stabilizing Atg7 in diabetic NP cells; while Atg7, but not HuR, may serve as a potential therapeutic target for DB‐IVDD. With high‐glucose treatment, the expression of HuR is decreased, which induces autophagy inactivation and increased senescence. Mechanistic study reveals that HuR regulates Atg7 expression through binding to Atg7 AU‐rich element and adjusting its mRNA stability
登录
查看更多内容
影响因子：
2.3
作者：
Kong JG;Park JB;Lee D;Park EY
通讯作者：
Park EY
影响因子：
16
作者：
Mukherjee N;Corcoran DL;Nusbaum JD;Reid DW;Georgiev S;Hafner M;Ascano M Jr;Tuschl T;Ohler U;Keene JD
通讯作者：
Keene JD
影响因子：
11.4
作者：
Song, Xiuzu;Narzt, Marie Sophie;Nagelreiter, Ionela Mariana;Hohensinner, Philipp;Terlecki-Zaniewicz, Lucia;Tschachler, Erwin;Grillari, Johannes;Gruber, Florian
通讯作者：
Gruber, Florian
影响因子：
12.8
作者：
Jin H;Zhang Z;Wang C;Tang Q;Wang J;Bai X;Wang Q;Nisar M;Tian N;Wang Q;Mao C;Zhang X;Wang X
通讯作者：
Wang X
影响因子：
64.8
作者：
Garcia-Prat, Laura;Martinez-Vicente, Marta;Munoz-Canoves, Pura
通讯作者：
Munoz-Canoves, Pura