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醛固酮受体与胚胎干细胞模型:分子研究进展及其与病理生理学的相关性。

Mineralocorticoid receptor and embryonic stem cell models: molecular insights and pathophysiological relevance.

机构信息

INSERM U693, Faculté de Médecine Paris-Sud 11, 63 rue Gabriel Péri, Le Kremlin-Bicêtre Cedex, France.

出版信息

Mol Cell Endocrinol. 2012 Mar 24;350(2):216-22. doi: 10.1016/j.mce.2011.06.036. Epub 2011 Jul 13.

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.

摘要

醛固酮受体(MR)信号对于许多生理过程至关重要,并与紧密上皮、中枢神经系统和心血管系统等多种病理状况有关。几十年来,人们一直在使用动物和细胞模型以及临床研究来研究 MR 的多效性作用。在此,我们回顾和阐述了一种最近出现的策略在分析 MR 信号复杂性方面的应用:从野生型或转基因 MR 过表达动物中衍生和分化出的小鼠胚胎干细胞(ES)细胞模型。未分化的 ES 细胞被分化为心肌细胞、神经元和脂肪细胞,这些细胞类型是 MR 的重要病理生理靶标。这些方法已经为我们提供了关于 MR 对心肌细胞收缩和离子通道重塑、神经元 MR 表达的调控及其对神经元存活的积极作用的新见解。分化的 ES 细胞模型因此构成了进一步解析细胞特异性 MR 作用的分子机制的强大而有前途的工具。

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