RGD Reference Report - Transcription suppression of thromboxane receptor gene by peroxisome proliferator-activated receptor-gamma via an interaction with Sp1 in vascular smooth muscle cells. - Rat Genome Database

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Transcription suppression of thromboxane receptor gene by peroxisome proliferator-activated receptor-gamma via an interaction with Sp1 in vascular smooth muscle cells.

Authors: Sugawara, A  Uruno, A  Kudo, M  Ikeda, Y  Sato, K  Taniyama, Y  Ito, S  Takeuchi, K 
Citation: Sugawara A, etal., J Biol Chem 2002 Mar 22;277(12):9676-83.
RGD ID: 619549
Pubmed: PMID:11777901   (View Abstract at PubMed)
DOI: DOI:10.1074/jbc.M104560200   (Journal Full-text)

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)-gamma, has recently been reported to be expressed in VSMCs. Here we examined a role of PPAR-gamma in TXR gene expression in VSMCs. PPAR-gamma ligands 15-deoxy-Delta(12,14)-prostaglandin J(2) and troglitazone reduced TXR mRNA expression levels as well as cell growth as assessed by [(3)H]thymidine incorporation. Transcriptional activity of the TXR gene promoter was suppressed with PPAR-gamma ligands, and the suppression was augmented further by PPAR-gamma 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-gamma, and the formation of a Sp1 small middle dotDNA complex was inhibited either by coincubation with PPAR-gamma or PPAR-gamma ligand treatment of VSMCs. Moreover, glutathione S-transferase pull-down assays demonstrated a direct interaction between PPAR-gamma and Sp1. In conclusion, PPAR-gamma suppresses TXR gene transcription via an interaction with Sp1. PPAR-gamma may possibly have an antiatherosclerotic action by inhibiting TXR gene expression in VSMCs.

Objects referenced in this article
Gene Pparg peroxisome proliferator-activated receptor gamma Rattus norvegicus
Gene Tbxa2r thromboxane A2 receptor Rattus norvegicus

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