| First Author | Kim JH | Year | 2015 |
| Journal | Arterioscler Thromb Vasc Biol | Volume | 35 |
| Issue | 11 | Pages | 2384-90 |
| PubMed ID | 26404484 | Mgi Jnum | J:242111 |
| Mgi Id | MGI:5904424 | Doi | 10.1161/ATVBAHA.115.306102 |
| Citation | Kim JH, et al. (2015) Estrogen-Related Receptor gamma Plays a Key Role in Vascular Calcification Through the Upregulation of BMP2 Expression. Arterioscler Thromb Vasc Biol 35(11):2384-90 |
| abstractText | OBJECTIVE: Vascular calcification which refers to ectopic mineralization in vascular cells is associated with several conditions, such as chronic kidney disease, atherosclerosis, and diabetes mellitus. Estrogen-related receptor (ERR)gamma is a member of the orphan nuclear receptor superfamily, which plays diverse roles in regulating homeostatic and metabolic processes. However, the role of ERRgamma in vascular calcification has not been investigated to date. The aim of the present study was to examine the role of ERRgamma in vascular calcification. APPROACH AND RESULTS: Vascular calcification was induced by treating rat aortic vascular smooth muscle cells with calcification medium. ERRgamma expression in vascular smooth muscle cells was induced during calcification medium-induced vascular calcification. Adenovirus-mediated overexpression of ERRgamma in vascular smooth muscle cells resulted in the upregulation of the expression of osteogenic genes, including runt-related transcription factor 2, osteopontin, and Msx2, and the downregulation of alpha-smooth muscle actin. Adenovirus-mediated overexpression of ERRgamma induced bone morphogenetic protein 2 (BMP2) expression, leading to increased phosphorylation of the intracellular BMP2 effector proteins SMAD1/5/8. Collectively, these data suggested that ERRgamma promotes dedifferentiation of vascular smooth muscle cells to an osteogenic phenotype during the vascular calcification process. Inhibition of endogenous ERRgamma expression or activity using a specific siRNA or the selective inverse agonist GSK5182 attenuated vascular calcification and osteogenic gene expression in vitro and in vivo. CONCLUSIONS: The present results indicate that ERRgamma plays a key role in vascular calcification by upregulating the BMP2 signaling pathway, suggesting that inhibition of ERRgamma is a potential therapeutic strategy for the prevention of vascular calcification. |
