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Published on: August 23, 2016
Mineralocorticoid receptor and embryonic stem cell models: molecular insights and pathophysiological relevance
Damien Le Menuet1, Mathilde Munier, Giulia Campostrini
1INSERM U693, Faculté de Médecine Paris-Sud 11, 63 rue Gabriel Péri, Le Kremlin-Bicêtre Cedex, France. damien.le-menuet@u-psud.fr
Abstract:
Mineralocorticoid receptor (MR) signaling is pivotal for numerous physiological processes and implicated in various pathological conditions concerning among others, tight epithelia, central nervous and cardiovascular systems. For decades, the pleiotropic actions of MR have been investigated using animal and cellular models as well as by clinical studies. Here is reviewed and contextualized the utilization of a strategy that recently emerged to analyze the complexity of MR signaling: the derivation and differentiation of mouse embryonic stem (ES) cell models. ES cells were derived from wild-type or transgenic MR overexpressing animals. Undifferentiated ES cells were differentiated into cardiomyocytes, neurons and adipocytes, these cell types being important pathophysiological targets of MR. These approaches have already brought new insights concerning MR effect on cardiomyocyte contractility and ionic channel remodeling, in the regulation of neuronal MR expression and its positive role on neuron survival. Differentiated ES cell models thus constitute powerful and promising tools to further decipher the molecular mechanisms of cell-specific MR actions.
Insights
Mouse embryonic stem (ES) cells offer a new way to study mineralocorticoid receptor (MR) signaling. Differentiated ES cells provide insights into MR
Area of Science:
- Endocrinology and Molecular Biology
Background:
- Mineralocorticoid receptor (MR) signaling is crucial for physiological functions and implicated in diseases affecting epithelia, nervous, and cardiovascular systems.
- Traditional research methods include animal models, cellular studies, and clinical investigations.
- Understanding the complex, cell-specific actions of MR remains a challenge.
Purpose of the Study:
- To review and contextualize the use of mouse embryonic stem (ES) cell models for analyzing MR signaling complexity.
- To highlight the potential of ES cell-derived models in understanding cell-specific MR functions.
Main Methods:
- Derivation of ES cells from wild-type and MR-overexpressing transgenic mice.
- Differentiation of undifferentiated ES cells into cardiomyocytes, neurons, and adipocytes.
- Analysis of MR's role in these differentiated cell types.
Main Results:
- ES cell models have provided new insights into MR's effects on cardiomyocyte contractility and ion channel remodeling.
- These models revealed MR's role in regulating neuronal MR expression and promoting neuron survival.
- The study contextualizes the utility of ES cell-derived models for MR research.
Conclusions:
- Differentiated mouse ES cell models are powerful tools for investigating MR signaling.
- These models offer a promising approach to deciphering the molecular mechanisms of cell-specific MR actions.
- ES cell-derived models advance the study of MR in cardiovascular, neuronal, and other target systems.

