Identification of a peroxisome proliferator responsive element (PPRE)-like cis-element in mouse plasminogen activator inhibitor-1 gene promoter

• Published in: Biochemical and biophysical research communications 2006-09, Vol.347 (3), p.821-826
• Main Authors: Chen, Jie-Gen, Li, Xi, Huang, Hai-Yan, Liu, Hong-Lei, Liu, De-Guo, Song, Tan-Jing, Ma, Chun-Gu, Ma, Duan, Song, Hou-Yan, Tang, Qi-Qun
• Format: Article
• Language: English
• Subjects: 3T3-L1; 3T3-L1 Cells; 60 APPLIED LIFE SCIENCES; Adipocytes - cytology; Adipocytes - metabolism; ADIPOSE TISSUE; Animals; ANTIBODIES; Cell Differentiation; DNA; GENES; LIGANDS; METABOLIC DISEASES; MICE; MUTATIONS; PATHOGENESIS; Peroxisome proliferator responsive element; Peroxisome proliferator-activated receptor γ; Peroxisome Proliferators - metabolism; Pioglitazone; PLASMINOGEN; Plasminogen Activator Inhibitor 1 - genetics; Plasminogen Activator Inhibitor 1 - metabolism; Plasminogen activator inhibitor-1; PPAR gamma - genetics; PPAR gamma - metabolism; Promoter Regions, Genetic - genetics; PROMOTERS; RECEPTORS; Response Elements; Transcription, Genetic - genetics
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2006.06.170

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 γ (PPARγ). 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 PPARγ antibody. Mutation of this PPRE-like cis-element can abolish the transactivation of mouse PAI-1 promoter mediated by PPARγ. Specific PPARγ ligand Pioglitazone can significantly induce the PAI-1 expression, and stimulate the secretion of PAI-1 into medium.