Identification of a peroxisome proliferator responsive element (PPRE)-like cis-element in mouse plasminogen activator inhibitor-1 gene promoter.
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.
Chen
Jie-Gen
JG
Key Laboratory of Molecular Medicine, Ministry of Education, Fudan University Shanghai Medical School, Shanghai, PR China.
Li
Xi
X
Huang
Hai-Yan
HY
Liu
Hong-Lei
HL
Liu
De-Guo
DG
Song
Tan-Jing
TJ
Ma
Chun-Gu
CG
Ma
Duan
D
Song
Hou-Yan
HY
Tang
Qi-Qun
QQ
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
D008024:Ligands; D047495:PPAR gamma; D020025:Peroxisome Proliferators; D017395:Plasminogen Activator Inhibitor 1