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

A modified suppression subtractive hybridization assay was performed to uncover genes induced by all-trans retinoic acid in cultured smooth muscle cells (SMC). Northern blotting studies confirmed the induction of 14 genes, many of which have heretofore been unrecognized as retinoid-inducible. Temporal expression and cycloheximide studies allowed us to categorize these genes as either immediate-early (LOX-1, endolyn, Stoned B/TFIIAα/β-like factor, Src Suppressed C Kinase Substrate, and tissue transglutaminase) or delayed (cathepsin-L, ceruloplasmin, epithelin, importin α, α₈-integrin, lactate dehydrogenase B, retinol dehydrogenase, spermidine/spermine N¹-acetyltransferase, and VCAM-1) retinoid-response genes. A survey of rat tissues showed two of the genes (tissue transglutaminase and α₈-integrin) to be highly restricted to vascular tissue. In situ hybridization verified expression of both tissue transglutaminase and α₈-integrin to SMC in balloon-injured rat carotid artery. These findings unveil a new retinoid-response gene set that should be exploited to define molecular pathways involved in the antagonistic effects of retinoids on SMC growth and neointimal formation.