RNA-Binding Protein HuR Suppresses Inflammation and Promotes Extracellular Matrix Homeostasis via NKRF in Intervertebral Disc Degeneration.
RNA-Binding Protein HuR Suppresses Inflammation and Promotes Extracellular Matrix Homeostasis via NKRF in Intervertebral Disc Degeneration.
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RNA 结合蛋白 HuR 在椎间盘退变中通过 NKRF 抑制炎症并促进细胞外基质稳态
DOI：
10.3389/fcell.2020.611234
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发表时间：
2020
影响因子：
5.5
通讯作者：
Zhang X
中科院分区：
文献类型：
--
作者：
Shao Z;Tu Z;Shi Y;Li S;Wu A;Wu Y;Tian N;Sun L;Pan Z;Chen L;Gao W;Zhou Y;Wang X;Zhang X
据报道，椎间盘退变（IVDD）是腰痛的主要原因。研究表明，IVDD可能在转录水平上失调;然而，是否涉及转录后调控仍然是未知的。本研究旨在阐明人抗原R（HuR），一种参与转录后调控的RNA结合蛋白，在IVDD中的作用。结果显示，退变髓核组织中HuR表达降低，TNF-α处理髓核细胞中HuR表达也降低。HuR的下调可能导致TNF-α处理的NP细胞中炎症和细胞外基质（ECM）降解增加;然而，这些作用在HuR过表达的NP细胞中未逆转。NF-κB信号通路的抑制减弱HuR缺陷型NP细胞中的炎症和ECM降解。机制研究表明，HuR通过与其富含AU的元件结合促进NKRF mRNA的稳定性，并且上调NKRF抑制HuR缺陷的NP细胞中的炎症和ECM降解。此外，我们发现，NKRF，而不是HuR，过表达改善了大鼠体内IVDD的过程。总之，HuR通过稳定NKRF和抑制NF-κB信号通路抑制NP细胞中的炎症和ECM降解; NKRF而不是HuR可能作为IVDD的潜在治疗靶点。
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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影响因子：
6.2
作者：
Ke, Ke;Chen, Tim (Hung-Po);Abu-Amer, Yousef
通讯作者：
Abu-Amer, Yousef
影响因子：
5.6
作者：
Jha P;Das H
通讯作者：
Das H
影响因子：
39.3
作者：
Liu T;Zhang L;Joo D;Sun SC
通讯作者：
Sun SC
DOI：
10.1073/pnas.1905172116
发表时间：
2019-08-27
影响因子：
11.1
作者：
Mubaid, Souad;Ma, Jennifer F.;Gallouzi, Imed-Eddine
通讯作者：
Gallouzi, Imed-Eddine
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