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Role for miR-204 in human pulmonary arterial hypertension
Pulmonary arterial hypertension (PAH) is characterized by enhanced proliferation and reduced apoptosis of pulmonary artery smooth muscle cells (PASMCs). Because microRNAs have been recently implicated in the regulation of cell proliferation and apoptosis, we hypothesized that these regulatory molecu...
Autores principales: | , , , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3058572/ https://www.ncbi.nlm.nih.gov/pubmed/21321078 http://dx.doi.org/10.1084/jem.20101812 |
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author | Courboulin, Audrey Paulin, Roxane Giguère, Nellie J. Saksouk, Nehmé Perreault, Tanya Meloche, Jolyane Paquet, Eric R. Biardel, Sabrina Provencher, Steeve Côté, Jacques Simard, Martin J. Bonnet, Sébastien |
author_facet | Courboulin, Audrey Paulin, Roxane Giguère, Nellie J. Saksouk, Nehmé Perreault, Tanya Meloche, Jolyane Paquet, Eric R. Biardel, Sabrina Provencher, Steeve Côté, Jacques Simard, Martin J. Bonnet, Sébastien |
author_sort | Courboulin, Audrey |
collection | PubMed |
description | Pulmonary arterial hypertension (PAH) is characterized by enhanced proliferation and reduced apoptosis of pulmonary artery smooth muscle cells (PASMCs). Because microRNAs have been recently implicated in the regulation of cell proliferation and apoptosis, we hypothesized that these regulatory molecules might be implicated in the etiology of PAH. In this study, we show that miR-204 expression in PASMCs is down-regulated in both human and rodent PAH. miR-204 down-regulation correlates with PAH severity and accounts for the proliferative and antiapoptotic phenotypes of PAH-PASMCs. STAT3 activation suppresses miR-204 expression, and miR-204 directly targets SHP2 expression, thereby SHP2 up-regulation, by miR-204 down-regulation, activates the Src kinase and nuclear factor of activated T cells (NFAT). STAT3 also directly induces NFATc2 expression. NFAT and SHP2 were needed to sustain PAH-PASMC proliferation and resistance to apoptosis. Finally, delivery of synthetic miR-204 to the lungs of animals with PAH significantly reduced disease severity. This study uncovers a new regulatory pathway involving miR-204 that is critical to the etiology of PAH and indicates that reestablishing miR-204 expression should be explored as a potential new therapy for this disease. |
format | Text |
id | pubmed-3058572 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-30585722011-09-14 Role for miR-204 in human pulmonary arterial hypertension Courboulin, Audrey Paulin, Roxane Giguère, Nellie J. Saksouk, Nehmé Perreault, Tanya Meloche, Jolyane Paquet, Eric R. Biardel, Sabrina Provencher, Steeve Côté, Jacques Simard, Martin J. Bonnet, Sébastien J Exp Med Article Pulmonary arterial hypertension (PAH) is characterized by enhanced proliferation and reduced apoptosis of pulmonary artery smooth muscle cells (PASMCs). Because microRNAs have been recently implicated in the regulation of cell proliferation and apoptosis, we hypothesized that these regulatory molecules might be implicated in the etiology of PAH. In this study, we show that miR-204 expression in PASMCs is down-regulated in both human and rodent PAH. miR-204 down-regulation correlates with PAH severity and accounts for the proliferative and antiapoptotic phenotypes of PAH-PASMCs. STAT3 activation suppresses miR-204 expression, and miR-204 directly targets SHP2 expression, thereby SHP2 up-regulation, by miR-204 down-regulation, activates the Src kinase and nuclear factor of activated T cells (NFAT). STAT3 also directly induces NFATc2 expression. NFAT and SHP2 were needed to sustain PAH-PASMC proliferation and resistance to apoptosis. Finally, delivery of synthetic miR-204 to the lungs of animals with PAH significantly reduced disease severity. This study uncovers a new regulatory pathway involving miR-204 that is critical to the etiology of PAH and indicates that reestablishing miR-204 expression should be explored as a potential new therapy for this disease. The Rockefeller University Press 2011-03-14 /pmc/articles/PMC3058572/ /pubmed/21321078 http://dx.doi.org/10.1084/jem.20101812 Text en © 2011 Courboulin et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/). |
spellingShingle | Article Courboulin, Audrey Paulin, Roxane Giguère, Nellie J. Saksouk, Nehmé Perreault, Tanya Meloche, Jolyane Paquet, Eric R. Biardel, Sabrina Provencher, Steeve Côté, Jacques Simard, Martin J. Bonnet, Sébastien Role for miR-204 in human pulmonary arterial hypertension |
title | Role for miR-204 in human pulmonary arterial hypertension |
title_full | Role for miR-204 in human pulmonary arterial hypertension |
title_fullStr | Role for miR-204 in human pulmonary arterial hypertension |
title_full_unstemmed | Role for miR-204 in human pulmonary arterial hypertension |
title_short | Role for miR-204 in human pulmonary arterial hypertension |
title_sort | role for mir-204 in human pulmonary arterial hypertension |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3058572/ https://www.ncbi.nlm.nih.gov/pubmed/21321078 http://dx.doi.org/10.1084/jem.20101812 |
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