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MiR-202-3p regulates interleukin-1β-induced expression of matrix metalloproteinase 1 in human nucleus pulposus.
Gene. 2019 Mar 01; 687:156-165.GENE

Abstract

MicroRNAs (miRNAs), small noncoding RNA molecules, have emerged as important factors during intervertebral disc degeneration. This study was to determine whether miR-202-3p regulates interleukin-1β (IL-1β)-induced expression of matrix metalloproteinase 1 (MMP-1) in human nucleus pulposus (NP) cells. Human NP cells were stimulated with IL-1β in vitro. MicroRNA arrays were used to determine the expression profile of 1971 human miRNAs and the miRNAs targets were identified using bioinformatics. In IL-1β-stimulated NP cells, 10 microRNAs were down-regulated, 2 microRNAs were up-regulated. There was a significant reduction in hsa-miR-202-3p (miR-202-3p) expression in the severe degenerative disc compared with mild degenerative disc. Down-regulation of miR-202-3p expression by IL-1β was correlated with up-regulation of MMP-1 expression in human NP cells. IL-1β-induced activation of MAP kinase (MAPK) and nuclear factor-κB (NF-κB) decreased miR-202-3p expression and induced MMP-1 expression. MiR-202-3p suppressed IL-1β-induced MMP-1 production. Conversely, treatment with anti-miR-202-3p remarkably increased MMP-1 production. In addition, mutation of the miR-202-3p binding site in the 3'-UTR of MMP-1 mRNA abolished miR-202-3p-mediated repression of reporter activity. Functional analysis showed that miR-202-3p could decrease type II collagen degradation, whereas overexpression of MMP-1 by Lentiviral-shMMP-1 abolished the effect of miR-202-3p on type II collagen degradation. These results suggest that miR-202-3p is an important regulator of MMP-1 in human nucleus pulposus and may contribute to the development of intervertebral disc degeneration.

Authors+Show Affiliations

Department of Orthopedics, Changzheng Hospital, Second Military Medical University of China, Shanghai, China.Department of Orthopedics, Changzheng Hospital, Second Military Medical University of China, Shanghai, China.Department of Orthopedics, Changzheng Hospital, Second Military Medical University of China, Shanghai, China.Department of Orthopedics, Forth People's Hospital, Changde, China.Department of Orthopedics, Changzheng Hospital, Second Military Medical University of China, Shanghai, China.Department of Orthopedics, Changzheng Hospital, Second Military Medical University of China, Shanghai, China.Department of Orthopedics, Changzheng Hospital, Second Military Medical University of China, Shanghai, China.Departments of Bioengineering, University of Illinois at Chicago, IL, USA; Jesse Brown Veterans Affairs Medical Center (JBVAMC) at Chicago, IL, USA.Department of Orthopedics, Changzheng Hospital, Second Military Medical University of China, Shanghai, China. Electronic address: charlieshi@smmu.edu.cn.Department of Orthopedics, Changzheng Hospital, Second Military Medical University of China, Shanghai, China. Electronic address: xjyespine@smmu.edu.cn.Department of Orthopedic Surgery, Mayo Clinic, Rochester, USA.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30458287

Citation

Shi, Changgui, et al. "MiR-202-3p Regulates Interleukin-1β-induced Expression of Matrix Metalloproteinase 1 in Human Nucleus Pulposus." Gene, vol. 687, 2019, pp. 156-165.
Shi C, Wu L, Lin W, et al. MiR-202-3p regulates interleukin-1β-induced expression of matrix metalloproteinase 1 in human nucleus pulposus. Gene. 2019;687:156-165.
Shi, C., Wu, L., Lin, W., Cai, Y., Zhang, Y., Hu, B., Gao, R., Im, H. J., Yuan, W., Ye, X., & van Wijnen, A. J. (2019). MiR-202-3p regulates interleukin-1β-induced expression of matrix metalloproteinase 1 in human nucleus pulposus. Gene, 687, 156-165. https://doi.org/10.1016/j.gene.2018.11.056
Shi C, et al. MiR-202-3p Regulates Interleukin-1β-induced Expression of Matrix Metalloproteinase 1 in Human Nucleus Pulposus. Gene. 2019 Mar 1;687:156-165. PubMed PMID: 30458287.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - MiR-202-3p regulates interleukin-1β-induced expression of matrix metalloproteinase 1 in human nucleus pulposus. AU - Shi,Changgui, AU - Wu,Lecheng, AU - Lin,Wenbo, AU - Cai,Yuanqi, AU - Zhang,Ying, AU - Hu,Bo, AU - Gao,Rui, AU - Im,Hee-Jeong, AU - Yuan,Wen, AU - Ye,Xiaojian, AU - van Wijnen,Andre J, Y1 - 2018/11/17/ PY - 2018/11/14/received PY - 2018/11/16/accepted PY - 2018/11/21/pubmed PY - 2019/1/19/medline PY - 2018/11/21/entrez KW - Interleukin-1β KW - Intervertebral disc degeneration KW - Matrix metalloproteinase 1 KW - MiR-202-3p KW - MicroRNA KW - Nucleus pulposus KW - Type II collagen SP - 156 EP - 165 JF - Gene JO - Gene VL - 687 N2 - MicroRNAs (miRNAs), small noncoding RNA molecules, have emerged as important factors during intervertebral disc degeneration. This study was to determine whether miR-202-3p regulates interleukin-1β (IL-1β)-induced expression of matrix metalloproteinase 1 (MMP-1) in human nucleus pulposus (NP) cells. Human NP cells were stimulated with IL-1β in vitro. MicroRNA arrays were used to determine the expression profile of 1971 human miRNAs and the miRNAs targets were identified using bioinformatics. In IL-1β-stimulated NP cells, 10 microRNAs were down-regulated, 2 microRNAs were up-regulated. There was a significant reduction in hsa-miR-202-3p (miR-202-3p) expression in the severe degenerative disc compared with mild degenerative disc. Down-regulation of miR-202-3p expression by IL-1β was correlated with up-regulation of MMP-1 expression in human NP cells. IL-1β-induced activation of MAP kinase (MAPK) and nuclear factor-κB (NF-κB) decreased miR-202-3p expression and induced MMP-1 expression. MiR-202-3p suppressed IL-1β-induced MMP-1 production. Conversely, treatment with anti-miR-202-3p remarkably increased MMP-1 production. In addition, mutation of the miR-202-3p binding site in the 3'-UTR of MMP-1 mRNA abolished miR-202-3p-mediated repression of reporter activity. Functional analysis showed that miR-202-3p could decrease type II collagen degradation, whereas overexpression of MMP-1 by Lentiviral-shMMP-1 abolished the effect of miR-202-3p on type II collagen degradation. These results suggest that miR-202-3p is an important regulator of MMP-1 in human nucleus pulposus and may contribute to the development of intervertebral disc degeneration. SN - 1879-0038 UR - https://www.unboundmedicine.com/medline/citation/30458287/MiR_202_3p_regulates_interleukin_1β_induced_expression_of_matrix_metalloproteinase_1_in_human_nucleus_pulposus_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0378-1119(18)31199-5 DB - PRIME DP - Unbound Medicine ER -