Cargando…

miRNA-221 Regulates Spinal Cord Injury-Induced Inflammatory Response through Targeting TNF-α Expression

OBJECTIVES: To investigate the roles of miR-221 in spinal cord injury (SCI) as well as the underlying mechanism. METHODS: A mouse model of SCI was generated and used to examine dynamic changes in grip strength of the mouse upper and lower limbs. The expression of miR-221 and tumor necrosis factor-α...

Descripción completa

Detalles Bibliográficos
Autores principales: Sun, Feng, Zhang, Haiwei, Huang, Tianwen, Shi, Jianhui, Wei, Tianli, Wang, Yansong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8049790/
https://www.ncbi.nlm.nih.gov/pubmed/33928162
http://dx.doi.org/10.1155/2021/6687963
_version_ 1783679485171728384
author Sun, Feng
Zhang, Haiwei
Huang, Tianwen
Shi, Jianhui
Wei, Tianli
Wang, Yansong
author_facet Sun, Feng
Zhang, Haiwei
Huang, Tianwen
Shi, Jianhui
Wei, Tianli
Wang, Yansong
author_sort Sun, Feng
collection PubMed
description OBJECTIVES: To investigate the roles of miR-221 in spinal cord injury (SCI) as well as the underlying mechanism. METHODS: A mouse model of SCI was generated and used to examine dynamic changes in grip strength of the mouse upper and lower limbs. The expression of miR-221 and tumor necrosis factor-α (TNF-α) was detected by RT-qPCR and Western blot. Levels of inflammation and oxidative stress in microglia cells of the injured mice overexpressing miR-221 were then measured by ELISA. Bioinformatics analysis and dual-luciferase reporter assay were conducted to identify the miR-221 target. RESULTS: We successfully constructed SCI mouse model. The results of qRT-PCR showed that miR-221 was gradually upregulated in the spinal cord tissue of mice in the SCI group with the prolonged injury time. At the same time, the mRNA and protein of TNF-α gradually decreased. We further confirmed through cell experiments that the inflammatory factors TNF-α and IL-6, as well as iNOS and eROS, were upregulated in spinal cord microglia cells of SCI mice, and upregulation of miR-122 can inhibit their expression. Finally, the luciferase reporter experiment confirmed that miR-122 targeted TNF-α. CONCLUSIONS: We present evidence that miR-221 promotes functional recovery of the injured spinal cord through targeting TNF-α, while alleviating inflammatory response and oxidative stress.
format Online
Article
Text
id pubmed-8049790
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Hindawi
record_format MEDLINE/PubMed
spelling pubmed-80497902021-04-28 miRNA-221 Regulates Spinal Cord Injury-Induced Inflammatory Response through Targeting TNF-α Expression Sun, Feng Zhang, Haiwei Huang, Tianwen Shi, Jianhui Wei, Tianli Wang, Yansong Biomed Res Int Research Article OBJECTIVES: To investigate the roles of miR-221 in spinal cord injury (SCI) as well as the underlying mechanism. METHODS: A mouse model of SCI was generated and used to examine dynamic changes in grip strength of the mouse upper and lower limbs. The expression of miR-221 and tumor necrosis factor-α (TNF-α) was detected by RT-qPCR and Western blot. Levels of inflammation and oxidative stress in microglia cells of the injured mice overexpressing miR-221 were then measured by ELISA. Bioinformatics analysis and dual-luciferase reporter assay were conducted to identify the miR-221 target. RESULTS: We successfully constructed SCI mouse model. The results of qRT-PCR showed that miR-221 was gradually upregulated in the spinal cord tissue of mice in the SCI group with the prolonged injury time. At the same time, the mRNA and protein of TNF-α gradually decreased. We further confirmed through cell experiments that the inflammatory factors TNF-α and IL-6, as well as iNOS and eROS, were upregulated in spinal cord microglia cells of SCI mice, and upregulation of miR-122 can inhibit their expression. Finally, the luciferase reporter experiment confirmed that miR-122 targeted TNF-α. CONCLUSIONS: We present evidence that miR-221 promotes functional recovery of the injured spinal cord through targeting TNF-α, while alleviating inflammatory response and oxidative stress. Hindawi 2021-04-07 /pmc/articles/PMC8049790/ /pubmed/33928162 http://dx.doi.org/10.1155/2021/6687963 Text en Copyright © 2021 Feng Sun et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Sun, Feng
Zhang, Haiwei
Huang, Tianwen
Shi, Jianhui
Wei, Tianli
Wang, Yansong
miRNA-221 Regulates Spinal Cord Injury-Induced Inflammatory Response through Targeting TNF-α Expression
title miRNA-221 Regulates Spinal Cord Injury-Induced Inflammatory Response through Targeting TNF-α Expression
title_full miRNA-221 Regulates Spinal Cord Injury-Induced Inflammatory Response through Targeting TNF-α Expression
title_fullStr miRNA-221 Regulates Spinal Cord Injury-Induced Inflammatory Response through Targeting TNF-α Expression
title_full_unstemmed miRNA-221 Regulates Spinal Cord Injury-Induced Inflammatory Response through Targeting TNF-α Expression
title_short miRNA-221 Regulates Spinal Cord Injury-Induced Inflammatory Response through Targeting TNF-α Expression
title_sort mirna-221 regulates spinal cord injury-induced inflammatory response through targeting tnf-α expression
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8049790/
https://www.ncbi.nlm.nih.gov/pubmed/33928162
http://dx.doi.org/10.1155/2021/6687963
work_keys_str_mv AT sunfeng mirna221regulatesspinalcordinjuryinducedinflammatoryresponsethroughtargetingtnfaexpression
AT zhanghaiwei mirna221regulatesspinalcordinjuryinducedinflammatoryresponsethroughtargetingtnfaexpression
AT huangtianwen mirna221regulatesspinalcordinjuryinducedinflammatoryresponsethroughtargetingtnfaexpression
AT shijianhui mirna221regulatesspinalcordinjuryinducedinflammatoryresponsethroughtargetingtnfaexpression
AT weitianli mirna221regulatesspinalcordinjuryinducedinflammatoryresponsethroughtargetingtnfaexpression
AT wangyansong mirna221regulatesspinalcordinjuryinducedinflammatoryresponsethroughtargetingtnfaexpression