RNA-Binding Protein HuR Suppresses Inflammation and Promotes Extracellular Matrix Homeostasis via NKRF in Intervertebral Disc Degeneration

• Published in: Frontiers in cell and developmental biology Vol. 8; p. 611234
• Main Authors: Shao, Zhenxuan, Tu, Zhuolong, Shi, Yifeng, Li, Sunlong, Wu, Aimin, Wu, Yaosen, Tian, Naifeng, Sun, Liaojun, Pan, Zongyou, Chen, Linwei, Gao, Weiyang, Zhou, Yifei, Wang, Xiangyang, Zhang, Xiaolei
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 25.11.2020
• Subjects: Cell and Developmental Biology; extracellular matrix; HuR; inflammation; intervertebral disc degeneration; NKRF; intervertebral disc degeneration; HuR; NKRF; inflammation; extracellular matrix
• ISSN: 2296-634X; 2296-634X
• DOI: 10.3389/fcell.2020.611234

Intervertebral disc degeneration (IVDD) has been reported to be a major cause of low back pain. Studies have demonstrated that IVDD may be dysregulated at the transcriptional level; however, whether post-transcriptional regulation is involved is still unknown. The current study aimed to illustrate the role of Human antigen R (HuR), an RNA binding protein involved in post-transcriptional regulation, in IVDD. The results showed that the expression of HuR was decreased in degenerative nucleus pulposus (NP) tissues as well as in TNF-α-treated NP cells. Downregulation of HuR may lead to increased inflammation and extracellular matrix (ECM) degradation in TNF-α-treated NP cells; however, these effects were not reversed in HuR overexpressed NP cells. Inhibition of the NF-κB signaling pathway attenuates inflammation and ECM degradation in HuR-deficient NP cells. A mechanism study showed that HuR prompted NKRF mRNA stability binding to its AU-rich elements, and upregulation of NKRF suppressed inflammation and ECM degradation in HuR-deficient NP cells. Furthermore, we found that NKRF, but not HuR, overexpression ameliorated the process of IVDD in rats . In conclusion, HuR suppressed inflammation and ECM degradation in NP cells stabilizing NKRF and inhibiting the NF-κB signaling pathway; NKRF, but not HuR, may serve as a potential therapeutic target for IVDD.