Open AccessRNA‐binding protein HuR suppresses senescence through Atg7 mediated autophagy activation in diabetic intervertebral disc degeneration
Author(s) -
Shao Zhenxuan,
Ni Libin,
Hu Sunli,
Xu Tianzhen,
Meftah Zaher,
Yu Zupo,
Tian Naifeng,
Wu Yaosen,
Sun Liaojun,
Wu Aimin,
Pan Zongyou,
Chen Linwei,
Gao Weiyang,
Zhou Yifei,
Zhang Xiaolei,
Wang Xiangyang
Publication year - 2021
Publication title -
cell proliferation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.647
H-Index - 74
eISSN - 1365-2184
pISSN - 0960-7722
DOI - 10.1111/cpr.12975
Subject(s) - autophagy , downregulation and upregulation , senescence , messenger rna , diabetes mellitus , biology , microbiology and biotechnology , apoptosis , endocrinology , gene , biochemistry
Objectives 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. Materials and Methods 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. Results 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. Conclusions 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.