To access the full text documents, please follow this link: http://hdl.handle.net/2445/149371
dc.contributor | Universitat de Barcelona |
---|---|
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, C. |
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 | 2020-02-04T11:55:22Z |
dc.date | 2020-02-04T11:55:22Z |
dc.date | 2015-06-25 |
dc.date | 2020-02-04T11:55:22Z |
dc.identifier.citation | 1754-8403 |
dc.identifier.citation | 654607 |
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 | 11 p. |
dc.format | application/pdf |
dc.language.iso | eng |
dc.publisher | The Company of Biologists |
dc.relation | Reproducció del document publicat a: https://doi.org/10.1242/dmm.020768 |
dc.relation | Disease Models & Mechanisms, 2015, vol. 8, num. 9, p. 1081-1091 |
dc.relation | https://doi.org/10.1242/dmm.020768 |
dc.rights | cc-by (c) Palomer Tarridas, Francesc Xavier et al., 2015 |
dc.rights | info:eu-repo/semantics/openAccess |
dc.rights | http://creativecommons.org/licenses/by/3.0/es |
dc.subject | Micro RNAs |
dc.subject | Cèl·lules |
dc.subject | Cor |
dc.subject | MicroRNAs |
dc.subject | Cells |
dc.subject | 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 |