Regulation of the murine α2(I) collagen promoter by retinoic acid and retinoid X receptors

Retinoic acid decreases collagen production by hepatic stellate cells. This study investigated the effects of retinoic acid receptor β (RARβ) and retinoid X receptor α (RXRα) on the regulation of the α2(I) collagen promoter. Retinoic acid and the RARβ and RXRα expression vectors suppressed the promoter in transfected stellate cells with maximal suppression obtained when combined. Mutation of the retinoic acid response element (RARE) at −879 to −874 (site 1) enhanced promoter activity and diminished but did not eliminate the suppression by RARβ and RXRα. Mutation of another RARE site (site 2), at −930 to −911, resulted in low activity that was inhibited by retinoic acid. Mutation of the AP-2-binding site enhanced promoter activity that was inhibited by retinoic acid. This study shows that the suppressive effect of retinoic acid on the promoter is maximal with a combination of RARβ and RXRα and occurs at more than one RARE site. The effect of retinoic acid is not mediated by AP-2.