Establishment and properties of a stable transfected epicardial cell line expressing a dominant negative retinoic acid receptor.

摘要

Retinoic acid (RA) is an important signaling molecule for the vertebrate embryo. Mouse embryos lacking the RA receptor RXRalpha fail to initiate a proliferative expansion of cardiomyocytes that leads to the hypoplastic ventricular chamber and die in utero although embryos undergo the early stages of heart morphogenesis. In this study, we investigated the underlying mechanistic basis of this phenotype. Previous observations showed that an established epicardial cell line (EMC cells) secretes trophic protein factors into conditioned media that stimulates thymidine incorporation in primay fetal cardiomyocytes, we further showed that an EMC subline constitutively expressing a dominant negative receptor construct failed to secrete activity into conditioned media. The epicardial-derived trophic signaling is induced by retinoic acid treatment. Therefore, we hypothesize that fetal epicardium secretes trophic factors to stimulate fetal cardiomyocyte proliferation and promote ventricular chamber morphogenesis. This mechanism is through the RXRalpha mediated retinoids action.