A novel retinoid-response gene set in vascular smooth muscle cells

A modified suppression subtractive hybridization assay was performed to unc over genes induced by all-trans retinoic acid in cultured smooth muscle cel ls (SMC). Northern blotting studies confirmed the induction of 14 genes, ma ny of which have heretofore been unrecognized as retinoid-inducible. Tempor al expression and cycloheximide studies allowed us to categorize these gene s as either immediate-early (LOX-1, endolyn, Stoned B/TFIIA alpha/beta -lik e factor, Src Suppressed C Kinase Substrate, and tissue transglutaminase) o r delayed (cathepsin-L, ceruloplasmin, epithelin, importin alpha, alpha (8) -integrin, lactate dehydrogenase B, retinol dehydrogenase, spermidine/sperm ine N-1-acetyltransferase, and VCAM-1) retinoid-response genes. A survey of rat tissues showed two of the genes (tissue transglutaminase and alpha (8) -integrin) to be highly restricted to vascular tissue. In situ hybridizatio n verified expression of both tissue transglutaminase and alpha (8)-integri n to SMC in balloon-injured rat carotid artery. These findings unveil a new retinoid-response gene set that should be exploited to define molecular pa thways involved in the antagonistic effects of retinoids on SMC growth and neointimal formation. (C) 2001 Academic Press.