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MicroRNA 148a Suppresses Tuberculous Fibrosis by Targeting NOX4 and POLDIP2
Extracellular matrix production by pleural mesothelial cells in response to Mycobacterium tuberculosis contributes to tuberculous fibrosis. NOX4 is involved in the pathogenesis of tuberculous fibrosis. In this study, we evaluated whether NOX4 gene-targeting microRNAs showed protective effects in tub...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8954251/ https://www.ncbi.nlm.nih.gov/pubmed/35328424 http://dx.doi.org/10.3390/ijms23062999 |
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author | Woo, Seong Ji Kim, Youngmi Jung, Harry Lee, Jae Jun Hong, Ji Young |
author_facet | Woo, Seong Ji Kim, Youngmi Jung, Harry Lee, Jae Jun Hong, Ji Young |
author_sort | Woo, Seong Ji |
collection | PubMed |
description | Extracellular matrix production by pleural mesothelial cells in response to Mycobacterium tuberculosis contributes to tuberculous fibrosis. NOX4 is involved in the pathogenesis of tuberculous fibrosis. In this study, we evaluated whether NOX4 gene-targeting microRNAs showed protective effects in tuberculosis fibrosis. TargetScan prediction software was used to identify candidate microRNAs that bind the 3′ UTRs of NOX4, and microRNA-148a (miR-148a) was selected as the best miRNA candidate. A repressed and forced expression assay in Met5A cells was performed to investigate the causal relationship between miR-148a and NOX4. The role of miR-148a in tuberculous pleural fibrosis was studied using a murine model of Mycobacterium bovis bacillus Calmette–Guérin (BCG) pleural infection. Heat-killed M. tuberculosis (HKMT) induces NOX4 and POLDIP2 expression. We demonstrated the inhibitory effect of miR-148a on NOX4 and POLDIP2 expression. The increased expression of miR-148a suppressed HKMT-induced collagen-1A synthesis in PMC cells. In the BCG pleurisy model, miR-148a significantly reduced fibrogenesis and epithelial mesenchymal transition. High levels of miR-148a in tuberculous pleural effusion can be interpreted as a self-limiting homeostatic response. Our data indicate that miR-148a may protect against tuberculous pleural fibrosis by regulating NOX4 and POLDIP2. |
format | Online Article Text |
id | pubmed-8954251 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-89542512022-03-26 MicroRNA 148a Suppresses Tuberculous Fibrosis by Targeting NOX4 and POLDIP2 Woo, Seong Ji Kim, Youngmi Jung, Harry Lee, Jae Jun Hong, Ji Young Int J Mol Sci Article Extracellular matrix production by pleural mesothelial cells in response to Mycobacterium tuberculosis contributes to tuberculous fibrosis. NOX4 is involved in the pathogenesis of tuberculous fibrosis. In this study, we evaluated whether NOX4 gene-targeting microRNAs showed protective effects in tuberculosis fibrosis. TargetScan prediction software was used to identify candidate microRNAs that bind the 3′ UTRs of NOX4, and microRNA-148a (miR-148a) was selected as the best miRNA candidate. A repressed and forced expression assay in Met5A cells was performed to investigate the causal relationship between miR-148a and NOX4. The role of miR-148a in tuberculous pleural fibrosis was studied using a murine model of Mycobacterium bovis bacillus Calmette–Guérin (BCG) pleural infection. Heat-killed M. tuberculosis (HKMT) induces NOX4 and POLDIP2 expression. We demonstrated the inhibitory effect of miR-148a on NOX4 and POLDIP2 expression. The increased expression of miR-148a suppressed HKMT-induced collagen-1A synthesis in PMC cells. In the BCG pleurisy model, miR-148a significantly reduced fibrogenesis and epithelial mesenchymal transition. High levels of miR-148a in tuberculous pleural effusion can be interpreted as a self-limiting homeostatic response. Our data indicate that miR-148a may protect against tuberculous pleural fibrosis by regulating NOX4 and POLDIP2. MDPI 2022-03-10 /pmc/articles/PMC8954251/ /pubmed/35328424 http://dx.doi.org/10.3390/ijms23062999 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Woo, Seong Ji Kim, Youngmi Jung, Harry Lee, Jae Jun Hong, Ji Young MicroRNA 148a Suppresses Tuberculous Fibrosis by Targeting NOX4 and POLDIP2 |
title | MicroRNA 148a Suppresses Tuberculous Fibrosis by Targeting NOX4 and POLDIP2 |
title_full | MicroRNA 148a Suppresses Tuberculous Fibrosis by Targeting NOX4 and POLDIP2 |
title_fullStr | MicroRNA 148a Suppresses Tuberculous Fibrosis by Targeting NOX4 and POLDIP2 |
title_full_unstemmed | MicroRNA 148a Suppresses Tuberculous Fibrosis by Targeting NOX4 and POLDIP2 |
title_short | MicroRNA 148a Suppresses Tuberculous Fibrosis by Targeting NOX4 and POLDIP2 |
title_sort | microrna 148a suppresses tuberculous fibrosis by targeting nox4 and poldip2 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8954251/ https://www.ncbi.nlm.nih.gov/pubmed/35328424 http://dx.doi.org/10.3390/ijms23062999 |
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