Regulation of α 2(I) collagen expression in stellate cells by retinoic acid and retinoid X receptors through interactions with their cofactors

Abstract

Retinoic acid (RA) suppresses α 2(I) collagen expression in hepatic stellate cells through the binding of retinoic acid receptor β (RARβ) and retinoid X receptor α (RXRα) to RA response elements (RAREs) in the α 2(I) collagen promoter. This study determined the influence of coactivators and corepressors to RARβ and RXRα on the regulation of the α 2(I) collagen promoter. The coactivators, steroid receptor coactivator-1 (SRC-1) and growth hormone receptor interacting protein-1 (GRIP-1), enhanced, while the nuclear receptor corepressor (N-CoR) abolished the inhibitory effect of RARβ and RXRα on the promoter activity. In the presence of RA, the coactivators SRC-1 and GRIP-1 formed complexes with RARβ and RXRα which are bound to an oligonucleotide specifying a RARE site in the promoter. In conclusion, this study shows that in the presence of retinoic acid, the coactivators SRC-1 and GRIP-1 augment, while the corepressor N-CoR abolishes, the suppressive effects of RARβ and RXRα on α 2(I) collagen promoter activity.