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

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 t...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7732619/
https://www.ncbi.nlm.nih.gov/pubmed/33330514
http://dx.doi.org/10.3389/fcell.2020.611234
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author 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
author_facet 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
author_sort Shao, Zhenxuan
collection PubMed
description 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 via 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 vivo. In conclusion, HuR suppressed inflammation and ECM degradation in NP cells via stabilizing NKRF and inhibiting the NF-κB signaling pathway; NKRF, but not HuR, may serve as a potential therapeutic target for IVDD.
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spelling pubmed-77326192020-12-15 RNA-Binding Protein HuR Suppresses Inflammation and Promotes Extracellular Matrix Homeostasis via NKRF in Intervertebral Disc Degeneration 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 Front Cell Dev Biol Cell and Developmental Biology 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 via 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 vivo. In conclusion, HuR suppressed inflammation and ECM degradation in NP cells via stabilizing NKRF and inhibiting the NF-κB signaling pathway; NKRF, but not HuR, may serve as a potential therapeutic target for IVDD. Frontiers Media S.A. 2020-11-25 /pmc/articles/PMC7732619/ /pubmed/33330514 http://dx.doi.org/10.3389/fcell.2020.611234 Text en Copyright © 2020 Shao, Tu, Shi, Li, Wu, Wu, Tian, Sun, Pan, Chen, Gao, Zhou, Wang and Zhang. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cell and Developmental Biology
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
RNA-Binding Protein HuR Suppresses Inflammation and Promotes Extracellular Matrix Homeostasis via NKRF in Intervertebral Disc Degeneration
title RNA-Binding Protein HuR Suppresses Inflammation and Promotes Extracellular Matrix Homeostasis via NKRF in Intervertebral Disc Degeneration
title_full RNA-Binding Protein HuR Suppresses Inflammation and Promotes Extracellular Matrix Homeostasis via NKRF in Intervertebral Disc Degeneration
title_fullStr RNA-Binding Protein HuR Suppresses Inflammation and Promotes Extracellular Matrix Homeostasis via NKRF in Intervertebral Disc Degeneration
title_full_unstemmed RNA-Binding Protein HuR Suppresses Inflammation and Promotes Extracellular Matrix Homeostasis via NKRF in Intervertebral Disc Degeneration
title_short RNA-Binding Protein HuR Suppresses Inflammation and Promotes Extracellular Matrix Homeostasis via NKRF in Intervertebral Disc Degeneration
title_sort rna-binding protein hur suppresses inflammation and promotes extracellular matrix homeostasis via nkrf in intervertebral disc degeneration
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7732619/
https://www.ncbi.nlm.nih.gov/pubmed/33330514
http://dx.doi.org/10.3389/fcell.2020.611234
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