{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T23:13:09Z","timestamp":1790637189300,"version":"4.1.0"},"reference-count":34,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2002,2,22]]},"abstract":"<jats:p>Peroxisome proliferator-activated receptor \u03b3 (PPAR\u03b3) is a member of the nuclear receptor superfamily that acts as a key player in adipocyte differentiation, glucose metabolism, and macrophage differentiation. Osteopontin (OPN), a component of extracellular matrix, is elevated during neointimal formation in the vessel wall and is synthesized by macrophages in atherosclerotic plaques. In the present study, we investigated the molecular mechanisms regulating OPN gene expression by PPAR\u03b3 in THP-1 cells, a cell line derived from human monocytic leukemia cells. Northern and Western blot analyses showed that exposure of THP-1 cells to PMA (phorbol 12-myristate 13-acetate) increases OPN mRNA and protein levels in a time-dependent manner. PMA-induced OPN expression was significantly decreased by troglitazone (Tro) and other PPAR\u03b3 ligands. Transient transfection assays of the human OPN promoter\/luciferase construct showed that PPAR\u03b3 represses OPN promoter activity, and the PPAR\u03b3-responsive region within the OPN promoter lies between \u22121000 and \u2212970 relative to the transcription start site. Site-specific mutation analysis and electrophoretic mobility shift assays indicated that a homeobox-like A\/T-rich sequence between \u2212990 and \u2212981, which functions as a binding site for PMA-induced nuclear factors other than PPAR\u03b3, mediates the repression of OPN expression by Tro. Furthermore, concatenated A\/T-rich sequences conferred the PPAR\u03b3 responsiveness on the heterologous promoter. Taken together, these data suggest that PPAR\u03b3 ligand inhibits OPN gene expression through the interference with the binding of nuclear factors to A\/T-rich sequence in THP-1 cells.<\/jats:p>","DOI":"10.1161\/hh0302.105098","type":"journal-article","created":{"date-parts":[[2002,7,28]],"date-time":"2002-07-28T23:16:47Z","timestamp":1027898207000},"page":"348-355","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":50,"title":["PPAR\u03b3 Ligand Inhibits Osteopontin Gene Expression Through Interference With Binding of Nuclear Factors to A\/T-Rich Sequence in THP-1 Cells"],"prefix":"10.1161","volume":"90","author":[{"given":"Yuko","family":"Oyama","sequence":"first","affiliation":[{"name":"From the Second Department of Internal Medicine (Y.O., N.A., M.K.), Gunma University School of Medicine, Maebashi, Gunma, Japan; and Department of Cardiovascular Medicine (R.N.), Graduate School of Medicine, University of Tokyo, Bunkyo-ku, Tokyo, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobuhiro","family":"Akuzawa","sequence":"additional","affiliation":[{"name":"From the Second Department of Internal Medicine (Y.O., N.A., M.K.), Gunma University School of Medicine, Maebashi, Gunma, Japan; and Department of Cardiovascular Medicine (R.N.), Graduate School of Medicine, University of Tokyo, Bunkyo-ku, Tokyo, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryozo","family":"Nagai","sequence":"additional","affiliation":[{"name":"From the Second Department of Internal Medicine (Y.O., N.A., M.K.), Gunma University School of Medicine, Maebashi, Gunma, Japan; and Department of Cardiovascular Medicine (R.N.), Graduate School of Medicine, University of Tokyo, Bunkyo-ku, Tokyo, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiko","family":"Kurabayashi","sequence":"additional","affiliation":[{"name":"From the Second Department of Internal Medicine (Y.O., N.A., M.K.), Gunma University School of Medicine, Maebashi, Gunma, Japan; and Department of Cardiovascular Medicine (R.N.), Graduate School of Medicine, University of Tokyo, Bunkyo-ku, Tokyo, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/362801a0"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.91.11.2844"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.83.23.8819"},{"key":"e_1_3_3_4_2","first-page":"293","volume":"149","year":"1996","unstructured":"Senger DR, Ledbetter SR, Claffey KP, Papadopoulos Sergiou A, Peruzzi CA, Detmar M. 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