Thromboxane (TX) A 2 exerts contraction and proliferation of vascular smooth muscle cells (VSMCs) via its specific membrane TX receptor (TXR) , possibly leading to the progression of atherosclerosis. A nuclear hormone receptor, peroxisome proliferator-activated receptor (PPAR)-␥, has recently been reported to be expressed in VSMCs. Here we examined a role of PPAR-␥ in TXR gene expression in VSMCs. PPAR-␥ ligands 15deoxy-⌬ 12,14 -prostaglandin J 2 and troglitazone reduced TXR mRNA expression

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... ls as well as cell growth as assessed by [ 3 H]thymidine incorporation. Transcriptional activity of the TXR gene promoter was suppressed with PPAR-␥ ligands, and the suppression was augmented further by PPAR-␥ overexpression. By deletion and mutation analyses, the transcription suppression was shown to be the result of a ؊22/؊7 GC box-related sequence (upstream of transcription start site). Electrophoretic mobility shift assays also showed that the sequence was bound by Sp1 but not by PPAR-␥, and the formation of a Sp1⅐DNA complex was inhibited either by coincubation with PPAR-␥ or PPAR-␥ ligand treatment of VSMCs. Moreover, glutathione S-transferase pulldown assays demonstrated a direct interaction between PPAR-␥ and Sp1. In conclusion, PPAR-␥ suppresses TXR gene transcription via an interaction with Sp1. PPAR-␥ may possibly have an antiatherosclerotic action by inhibiting TXR gene expression in VSMCs.