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 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.

• Authors: 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
• Journal: Scientific reports (Sci Rep) Vol. 7 Issue 1 Pg. 8898 (08 21 2017) ISSN: 2045-2322 [Electronic] England
• PMID: 28827743 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers
• Cardiotonic Agents
• MIRN125 microRNA, rat
• MIRN139 microRNA, rat
• MIRN324 microRNA, rat
• MicroRNAs
• Urocortins

Topics

• Animals
• Biomarkers
• Cardiotonic Agents (pharmacology)
• Disease Models, Animal
• Gene Expression Profiling
• Gene Expression Regulation (drug effects)
• Hemodynamics
• Male
• MicroRNAs (genetics, metabolism)
• Myocardial Reperfusion Injury (genetics, metabolism, physiopathology)
• Myocytes, Cardiac (metabolism)
• RNA Interference
• Rats
• Urocortins (metabolism, pharmacology)