title: Identification of a peroxisome proliferator responsive element (PPRE)-like cis-element in mouse plasminogen activator inhibitor-1 gene promoter.
abstract: PAI-1 is expressed and secreted by adipose tissue which may mediate the pathogenesis of obesity-associated cardiovascular complications. Evidence is presented in this report that PAI-1 is not expressed by preadipocyte, but significantly induced during 3T3-L1 adipocyte differentiation and the PAI-1 expression correlates with the induction of peroxisome proliferator-activated receptor gamma (PPARgamma). A peroxisome proliferator responsive element (PPRE)-like cis-element (-206TCCCCCATGCCCT-194) is identified in the mouse PAI-1 gene promoter by electrophoretic mobility shift assay (EMSA) combined with transient transfection experiments; the PPRE-like cis-element forms a specific DNA-protein complex only with adipocyte nuclear extracts, not with preadipocyte nuclear extracts; the DNA-protein complex can be totally competed away by non-labeled consensus PPRE, and can be supershifted with PPARgamma antibody. Mutation of this PPRE-like cis-element can abolish the transactivation of mouse PAI-1 promoter mediated by PPARgamma. Specific PPARgamma ligand Pioglitazone can significantly induce the PAI-1 expression, and stimulate the secretion of PAI-1 into medium.
authors.affiliation: Key Laboratory of Molecular Medicine, Ministry of Education, Fudan University Shanghai Medical School, Shanghai, PR China.
authors.forename: Jie-Gen
authors.initials: JG
authors.lastname: Chen
authors.forename: Xi
authors.initials: X
authors.lastname: Li
authors.forename: Hai-Yan
authors.initials: HY
authors.lastname: Huang
authors.forename: Hong-Lei
authors.initials: HL
authors.lastname: Liu
authors.forename: De-Guo
authors.initials: DG
authors.lastname: Liu
authors.forename: Tan-Jing
authors.initials: TJ
authors.lastname: Song
authors.forename: Chun-Gu
authors.initials: CG
authors.lastname: Ma
authors.forename: Duan
authors.initials: D
authors.lastname: Ma
authors.forename: Hou-Yan
authors.initials: HY
authors.lastname: Song
authors.forename: Qi-Qun
authors.initials: QQ
authors.lastname: Tang
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation; D008024:Ligands; D051379:Mice; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D020025:Peroxisome Proliferators / Q000378:metabolism*; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics* / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D020218:Response Elements; D014158:Transcription, Genetic / Q000235:genetics
chemical_list: D008024:Ligands; D047495:PPAR gamma; D020025:Peroxisome Proliferators; D017395:Plasminogen Activator Inhibitor 1