| First Author | Kwon DH | Year | 2013 |
| Journal | J Mol Cell Cardiol | Volume | 65 |
| Pages | 88-97 | PubMed ID | 24083978 |
| Mgi Jnum | J:308150 | Mgi Id | MGI:6725958 |
| Doi | 10.1016/j.yjmcc.2013.09.011 | Citation | Kwon DH, et al. (2013) Estrogen-related receptor gamma induces cardiac hypertrophy by activating GATA4. J Mol Cell Cardiol 65:88-97 |
| abstractText | Estrogen-related receptor gamma (ERRgamma) is an orphan nuclear receptor that has biological roles mainly in metabolism and that controls metabolic switching in perinatal heart. In adult heart diseases, however, the functional roles of ERRgamma have not yet been elucidated. In the present study, we aimed to characterize the role of ERRgamma in cardiac hypertrophy. The functional roles of ERRgamma in the development of cardiac hypertrophy were examined in primary cultured cardiomyocytes and in animal models. ERRgamma expression was increased in hearts from human hypertrophic cardiomyopathy patients and in both cellular and animal models of cardiac hypertrophy. Transgenic overexpression in mouse heart as well as forced expression of ERRgamma in cardiomyocytes induced hypertrophic phenotypes. Knock-down of ERRgamma blocked agonist-induced hypertrophic phenotypes. ERRgamma bound directly to the proximal ERR-responsive element in the GATA4 promoter in a sequence-specific manner and thereby induced transcription. ERRgamma-induced hypertrophy was blocked by inhibition of GATA4. GSK-5182, an inverse agonist of ERRgamma, completely blocked cardiac hypertrophy in cardiomyocytes. It also prevented aortic banding-induced cardiac hypertrophy and fibrosis in mouse heart. These findings demonstrate a novel ERRgamma/GATA4 signal cascade in the development of cardiac hypertrophy and suggest GSK-5182 as a possible therapeutic. |
