Díaz, IgnacioCalderón-Sánchez, EvaToro, Raquel DelÁvila-Médina, Javierde Rojas-de Pedro, Eva SánchezDomínguez-Rodríguez, AlejandroRosado, Juan AntonioHmadcha, AbdelkrimOrdóñez, AntonioSmani, Tarik2023-01-252023-01-252017-08-21http://hdl.handle.net/10668/11525Urocortin 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.enAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/AnimalsBiomarkersCardiotonic AgentsDisease Models, AnimalGene Expression ProfilingGene Expression RegulationHemodynamicsMaleMicroRNAsMyocardial Reperfusion InjuryMyocytes, CardiacRNA InterferenceRatsUrocortinsresearch article28827743open access10.1038/s41598-017-09198-x2045-2322PMC5566224https://doi.org/10.1038/s41598-017-09198-xhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5566224/pdf