Regulation of α2(I) collagen expression in stellate cells by retinoic acid and retinoid X receptors through interactions with their cofactors

Retinoic acid (RA) suppresses α2(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 α2(I) collagen promoter. This study determined the influence of coactivators and corepressors to RARβ and RXRα on the regulation of the α2(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 α2(I) collagen promoter activity.