Retinoic acid signaling is directly activated in cardiomyocytes and protects mouse hearts from apoptosis after myocardial infarction
- Université Côte d'Azur, France
- IGBMC, France
Abstract
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 CreERT2 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 Aldh1a1/a2/a3 genes encoding RA-synthesizing enzymes leads to increased cardiomyocyte apoptosis in adults subjected to MI. RNA sequencing analysis reveals Tgm2 and Ace1, 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.
Data availability
RNA sequencing data have been deposited in GEO under accession code GSE161429
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Genome wide sequencing analysis of primary cardiomyocytes treated with all-trans retinoic acidNCBI Gene Expression Omnibus, GSE161429.
Article and author information
Author details
Lahiru Chamara Weerasinghe Arachchige
Stephen T Bradford
Funding
Fondation de France (00056856)
- Andreas Schedl
Fondation ARC pour la Recherche sur le Cancer (SL22020605297)
- Andreas Schedl
Agence Nationale de la Recherche (ANR-11-LABX-0028-01)
- Fabio Da Silva
- Andreas Schedl
Ligue Contre le Cancer (equipe labelisée 2018)
- Andreas Schedl
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All animal work was conducted according to national and international guidelines and was approved by the local ethics committee (PEA-NCE/2013/88).
Reviewing Editor
- Edward E Morrisey, University of Pennsylvania, United States
Version history
- Preprint posted: December 4, 2020 (view preprint)
- Received: March 14, 2021
- Accepted: October 7, 2021
- Accepted Manuscript published: October 8, 2021 (version 1)
- Version of Record published: October 21, 2021 (version 2)
Copyright
© 2021, Da Silva et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Retinoic acid signaling is directly activated in cardiomyocytes and protects mouse hearts from apoptosis after myocardial infarction
eLife 10:e68280.
https://doi.org/10.7554/eLife.68280
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