Regulation of α2(I) collagen expression in stellate cells by retinoic acid and retinoid X receptors through interactions with their cofactors
2004
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.
Keywords:
- Retinoid X receptor gamma
- Molecular biology
- Retinoid X receptor beta
- Retinoid X receptor alpha
- Retinoic acid receptor alpha
- Retinoic acid receptor gamma
- Cancer research
- Biochemistry
- Retinoic acid receptor
- Biology
- Retinoid X receptor
- Retinoic acid-inducible orphan G protein-coupled receptor
- Retinoic acid receptor beta
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