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DC Field | Value | Language |
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dc.contributor.author | Palomer Tarridas, Francesc Xavier | - |
dc.contributor.author | Capdevila Busquets, Eva | - |
dc.contributor.author | Botteri, Gaia | - |
dc.contributor.author | Davidson, Mercy M. | - |
dc.contributor.author | Rodríguez, Cristina | - |
dc.contributor.author | Martínez González, José | - |
dc.contributor.author | Vidal, Francisco, 1966- | - |
dc.contributor.author | Barroso Fernández, Emma | - |
dc.contributor.author | Chan, Tung O. | - |
dc.contributor.author | Feldman, Arthur M. | - |
dc.contributor.author | Vázquez Carrera, Manuel | - |
dc.date.accessioned | 2020-02-04T11:55:22Z | - |
dc.date.available | 2020-02-04T11:55:22Z | - |
dc.date.issued | 2015-06-25 | - |
dc.identifier.issn | 1754-8403 | - |
dc.identifier.uri | http://hdl.handle.net/2445/149371 | - |
dc.description.abstract | miR-146a is a microRNA whose transcript levels are induced in the heart upon activation of NF-kappaB, a transcription factor induced by pro-inflammatory molecules strongly related to the pathogenesis of cardiac disorders. The main goal of this study consisted in studying new roles of miR-146a in cardiac pathological processes caused by the pro-inflammatory cytokine TNF-alpha. Our results demonstrate that miR-146a transcript levels were sharply increased in cardiac ventricular tissue of transgenic mice with specific overexpression of TNF-alpha in the heart, and also in a cardiomyocyte cell line of human origin (AC16) exposed to TNF-alpha. Among all the in silico predicted miR-146a target genes, c-Fos mRNA and protein levels notably decreased after TNF-alpha treatment or miR-146a overexpression. These changes correlated with a diminution in the DNA-binding activity of AP-1, the c-Fos-containing transcription factor complex. Interestingly, AP-1 inhibition was accompanied by a reduction in matrix metalloproteinase (MMP)-9 mRNA levels in human cardiac cells. The specific regulation of this matrix metalloproteinase by miR-146a was further confirmed at the secretion and enzymatic activity levels, as well as after anti-miR-mediated miR-146a inhibition. The results reported here demonstrate that c-Fos is a direct target of miR-146a activity and that c-Fos/AP-1 pathway downregulation by miR-146a has the capacity to inhibit MMP-9 activity. Given that MMP-9 is an AP-1 target gene involved in cardiac remodeling, myocardial dysfunction and progression of heart failure, these findings suggest that miR-146a may be a new and promising therapeutic tool for treating cardiac disorders associated with enhanced inflammation in the heart. | - |
dc.format.extent | 11 p. | - |
dc.format.mimetype | application/pdf | - |
dc.language.iso | eng | - |
dc.publisher | The Company of Biologists | - |
dc.relation.isformatof | Reproducció del document publicat a: https://doi.org/10.1242/dmm.020768 | - |
dc.relation.ispartof | Disease Models & Mechanisms, 2015, vol. 8, num. 9, p. 1081-1091 | - |
dc.relation.uri | https://doi.org/10.1242/dmm.020768 | - |
dc.rights | cc-by (c) Palomer Tarridas, Francesc Xavier et al., 2015 | - |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/es | - |
dc.source | Articles publicats en revistes (Farmacologia, Toxicologia i Química Terapèutica) | - |
dc.subject.classification | Micro RNAs | - |
dc.subject.classification | Cèl·lules | - |
dc.subject.classification | Cor | - |
dc.subject.other | MicroRNAs | - |
dc.subject.other | Cells | - |
dc.subject.other | Heart | - |
dc.title | miR-146a targets Fos expression in human cardiac cells | - |
dc.type | info:eu-repo/semantics/article | - |
dc.type | info:eu-repo/semantics/publishedVersion | - |
dc.identifier.idgrec | 654607 | - |
dc.date.updated | 2020-02-04T11:55:22Z | - |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | - |
dc.identifier.pmid | 26112171 | - |
Appears in Collections: | Articles publicats en revistes (Farmacologia, Toxicologia i Química Terapèutica) Articles publicats en revistes (Institut de Biomedicina (IBUB)) |
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654607.pdf | 1.28 MB | Adobe PDF | View/Open |
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