Related Experiment Video
Updated: Jul 18, 2026
Assessing Cardiomyocyte Subtypes Following Transcription Factor-mediated Reprogramming of Mouse Embryonic Fibroblasts
Published on: March 22, 2017
Identification of corticosteroid-regulated genes in cardiomyocytes by serial analysis of gene expression
Olivier Muller1, Sylvain Pradervand, Stefan Berger
1Cardiology Service, University Hospital, CHUV, CH-1011 Lausanne, Switzerland.
Abstract:
Corticosteroids (aldosterone, cortisol/corticosterone) exert direct functional effects on cardiomyocytes. However, gene networks activated by corticosteroids in cardiomyocytes, as well as the involvement of the mineralocorticoid receptor (MR) vs the glucocorticoid receptor (GR) in these effects, remain largely unknown. Here we characterized the corticosteroid-dependent transcriptome in primary culture of neonatal mouse cardiomyocytes treated with 10(-6) M aldosterone, a concentration predicted to occupy both MR and GR. Serial analysis of gene expression revealed 101 aldosterone-regulated genes. The MR/GR specificity was characterized for one regulated transcript, namely ecto-ADP-ribosyltransferase-3 (Art3). Using cardiomyocytes from GR(null/null) or MR(null/null) mice we demonstrate that in GR(null/null) cardiomyocytes the response is abrogated, but it is fully maintained in MR(null/null) cardiomyocytes. We conclude that Art3 expression is regulated exclusively via the GR. Our study identifies a new set of corticosteroid-regulated genes in cardiomyocytes and demonstrates a new approach to studying the selectivity of MR- vs GR-dependent effects.
Insights
Corticosteroids regulate genes in heart cells, with the glucocorticoid receptor (GR) exclusively controlling Art3 expression. This study identifies new corticosteroid-regulated genes and a method for assessing mineralocorticoid receptor (MR) vs. GR effects.
Area of Science:
- Cardiology
- Molecular Biology
- Endocrinology
Background:
- Corticosteroids impact cardiomyocyte function.
- Gene networks activated by corticosteroids in cardiomyocytes are largely unknown.
- The roles of mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) in these effects are unclear.
Purpose of the Study:
- To characterize the corticosteroid-dependent transcriptome in cardiomyocytes.
- To determine the specific receptor (MR vs. GR) mediating these effects.
Main Methods:
- Primary culture of neonatal mouse cardiomyocytes treated with aldosterone.
- Serial analysis of gene expression.
- Utilized GR(null/null) and MR(null/null) mouse cardiomyocytes to assess receptor specificity.
Main Results:
- Identified 101 aldosterone-regulated genes.
- Ecto-ADP-ribosyltransferase-3 (Art3) expression was investigated for MR/GR specificity.
- Art3 regulation was abrogated in GR(null/null) cardiomyocytes but maintained in MR(null/null) cardiomyocytes, indicating exclusive GR control.
Conclusions:
- Aldosterone regulates a novel set of genes in cardiomyocytes.
- Art3 expression is exclusively mediated by the glucocorticoid receptor (GR).
- Developed a novel approach to differentiate MR- vs. GR-dependent effects in cardiomyocytes.
