miR-125a, miR-139 and miR-324 contribute to Urocortin protection against myocardial ischemia-reperfusion injury

Abstract Urocortin 1 and 2 (Ucn-1 and Ucn-2) have established protective actions against myocardial ischemia-reperfusion (I/R) injuries. However, little is known about their role in posttranscriptional regulation in the process of cardioprotection. Herein, we investigated whether microRNAs play a ro...

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Autores principales:	Ignacio Díaz, Eva Calderón-Sánchez, Raquel Del Toro, Javier Ávila-Médina, Eva Sánchez de Rojas-de Pedro, Alejandro Domínguez-Rodríguez, Juan Antonio Rosado, Abdelkrim Hmadcha, Antonio Ordóñez, Tarik Smani
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/4ebba404f4bc4c64b9e6bdb137991bce
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spelling	oai:doaj.org-article:4ebba404f4bc4c64b9e6bdb137991bce2021-12-02T16:06:22ZmiR-125a, miR-139 and miR-324 contribute to Urocortin protection against myocardial ischemia-reperfusion injury10.1038/s41598-017-09198-x2045-2322https://doaj.org/article/4ebba404f4bc4c64b9e6bdb137991bce2017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-09198-xhttps://doaj.org/toc/2045-2322Abstract Urocortin 1 and 2 (Ucn-1 and Ucn-2) have established protective actions against myocardial ischemia-reperfusion (I/R) injuries. However, little is known about their role in posttranscriptional regulation in the process of cardioprotection. Herein, we investigated whether microRNAs play a role in urocortin-induced cardioprotection. Administration of Ucn-1 and Ucn-2 at the beginning of reperfusion significantly restored cardiac function, as evidenced ex vivo in Langendorff-perfused rat hearts and in vivo in rat subjected to I/R. Experiments using microarray and qRT-PCR determined that the addition of Ucn-1 at reperfusion modulated the expression of several miRNAs with unknown role in cardiac protection. Ucn-1 enhanced the expression of miR-125a-3p, miR-324-3p; meanwhile it decreased miR-139-3p. Similarly, intravenous infusion of Ucn-2 in rat model of I/R mimicked the effect of Ucn-1 on miR-324-3p and miR-139-3p. The effect of Ucn-1 involves the activation of corticotropin-releasing factor receptor-2, Epac2 and ERK1/2. Moreover, the overexpression of miR-125a-3p, miR-324-3p and miR-139-3p promoted dysregulation of genes expression involved in cell death and apoptosis (BRCA1, BIM, STAT2), in cAMP and Ca2+ signaling (PDE4a, CASQ1), in cell stress (NFAT5, XBP1, MAP3K12) and in metabolism (CPT2, FoxO1, MTRF1, TAZ). Altogether, these data unveil a novel role of urocortin in myocardial protection, involving posttranscriptional regulation with miRNAs.Ignacio DíazEva Calderón-SánchezRaquel Del ToroJavier Ávila-MédinaEva Sánchez de Rojas-de PedroAlejandro Domínguez-RodríguezJuan Antonio RosadoAbdelkrim HmadchaAntonio OrdóñezTarik SmaniNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-14 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ignacio Díaz Eva Calderón-Sánchez Raquel Del Toro Javier Ávila-Médina Eva Sánchez de Rojas-de Pedro Alejandro Domínguez-Rodríguez Juan Antonio Rosado Abdelkrim Hmadcha Antonio Ordóñez Tarik Smani miR-125a, miR-139 and miR-324 contribute to Urocortin protection against myocardial ischemia-reperfusion injury
description	Abstract Urocortin 1 and 2 (Ucn-1 and Ucn-2) have established protective actions against myocardial ischemia-reperfusion (I/R) injuries. However, little is known about their role in posttranscriptional regulation in the process of cardioprotection. Herein, we investigated whether microRNAs play a role in urocortin-induced cardioprotection. Administration of Ucn-1 and Ucn-2 at the beginning of reperfusion significantly restored cardiac function, as evidenced ex vivo in Langendorff-perfused rat hearts and in vivo in rat subjected to I/R. Experiments using microarray and qRT-PCR determined that the addition of Ucn-1 at reperfusion modulated the expression of several miRNAs with unknown role in cardiac protection. Ucn-1 enhanced the expression of miR-125a-3p, miR-324-3p; meanwhile it decreased miR-139-3p. Similarly, intravenous infusion of Ucn-2 in rat model of I/R mimicked the effect of Ucn-1 on miR-324-3p and miR-139-3p. The effect of Ucn-1 involves the activation of corticotropin-releasing factor receptor-2, Epac2 and ERK1/2. Moreover, the overexpression of miR-125a-3p, miR-324-3p and miR-139-3p promoted dysregulation of genes expression involved in cell death and apoptosis (BRCA1, BIM, STAT2), in cAMP and Ca2+ signaling (PDE4a, CASQ1), in cell stress (NFAT5, XBP1, MAP3K12) and in metabolism (CPT2, FoxO1, MTRF1, TAZ). Altogether, these data unveil a novel role of urocortin in myocardial protection, involving posttranscriptional regulation with miRNAs.
format	article
author	Ignacio Díaz Eva Calderón-Sánchez Raquel Del Toro Javier Ávila-Médina Eva Sánchez de Rojas-de Pedro Alejandro Domínguez-Rodríguez Juan Antonio Rosado Abdelkrim Hmadcha Antonio Ordóñez Tarik Smani
author_facet	Ignacio Díaz Eva Calderón-Sánchez Raquel Del Toro Javier Ávila-Médina Eva Sánchez de Rojas-de Pedro Alejandro Domínguez-Rodríguez Juan Antonio Rosado Abdelkrim Hmadcha Antonio Ordóñez Tarik Smani
author_sort	Ignacio Díaz
title	miR-125a, miR-139 and miR-324 contribute to Urocortin protection against myocardial ischemia-reperfusion injury
title_short	miR-125a, miR-139 and miR-324 contribute to Urocortin protection against myocardial ischemia-reperfusion injury
title_full	miR-125a, miR-139 and miR-324 contribute to Urocortin protection against myocardial ischemia-reperfusion injury
title_fullStr	miR-125a, miR-139 and miR-324 contribute to Urocortin protection against myocardial ischemia-reperfusion injury
title_full_unstemmed	miR-125a, miR-139 and miR-324 contribute to Urocortin protection against myocardial ischemia-reperfusion injury
title_sort	mir-125a, mir-139 and mir-324 contribute to urocortin protection against myocardial ischemia-reperfusion injury
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/4ebba404f4bc4c64b9e6bdb137991bce
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miR-125a, miR-139 and miR-324 contribute to Urocortin protection against myocardial ischemia-reperfusion injury

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