Retinoic acid signaling is directly activated in cardiomyocytes and protects mouse hearts from apoptosis after myocardial infarction.
Fiche publication
Date publication
octobre 2021
Journal
eLife
Auteurs
Membres identifiés du Cancéropôle Est :
Dr DOLLE Pascal
Tous les auteurs :
Da Silva F, Jian Motamedi F, Weerasinghe Arachchige LC, Tison A, Bradford ST, Lefebvre J, Dolle P, Ghyselinck NB, Wagner KD, Schedl A
Lien Pubmed
Résumé
Retinoic acid (RA) is an essential signaling molecule for cardiac development and plays a protective role in the heart after myocardial infarction (MI). In both cases, the effect of RA signaling on cardiomyocytes, the principle cell type of the heart, has been reported to be indirect. Here we have developed an inducible murine transgenic RA-reporter line using CreER technology that permits lineage tracing of RA-responsive cells and faithfully recapitulates endogenous RA activity in multiple organs during embryonic development. Strikingly, we have observed a direct RA response in cardiomyocytes during mid-late gestation and after MI. Ablation of RA signaling through deletion of the genes encoding RA-synthesizing enzymes leads to increased cardiomyocyte apoptosis in adults subjected to MI. RNA sequencing analysis reveals and two genes with well-established links to cardiac repair as potential targets of RA signaling in primary cardiomyocytes, thereby providing novel links between the RA pathway and heart disease.
Mots clés
developmental biology, mouse, regenerative medicine, stem cells
Référence
Elife. 2021 Oct 8;10: