2. Academic Validation
  3. 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

  • Cell Prolif. 2021 Feb;54(2):e12975. doi: 10.1111/cpr.12975.
Zhenxuan Shao 1 2 3,  Libin Ni 1 2 3,  Sunli Hu 1 2 3,  Tianzhen Xu 1 4,  Zaher Meftah 1 2 3,  Zupo Yu 1 2 3,  Naifeng Tian 1 2 3,  Yaosen Wu 1 2 3,  Liaojun Sun 1 2 3,  Aimin Wu 1 2 3,  Zongyou Pan 5,  Linwei Chen 5,  Weiyang Gao 1 2 3,  Yifei Zhou 1 2 3,  Xiaolei Zhang 1 2 3,  Xiangyang Wang 1 2 3
Affiliations

Affiliations

  • 1 Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.
  • 2 Key Laboratory of Orthopaedics of Zhejiang Province, Wenzhou, China.
  • 3 The Second School of Medicine, Wenzhou Medical University, Wenzhou, China.
  • 4 Department of Orthopaedics, Zhuji People's Hospital of Zhejiang Province, China.
  • 5 Department of Orthopaedics, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.
PMID: 33372336 DOI: 10.1111/cpr.12975
Abstract

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.

Keywords

Atg7; HuR; autophagy; diabetes; intervertebral disc degeneration; senescence.

Figures
Products