The alteration of plasminogen activator inhibitor-1 expression by linoleic acid and fenofibrate in HepG2 cells.
The present study investigated the influence of linoleic acid and fenofibrate on plasminogen activator inhibitor-1 (PAI-1) expression in HepG2 cells and the mechanism possibly involved. Using gene recombination techniques, chloromycetin acetyltransferase (CAT) reporter gene plasmids containing nuclear factor-kappaB response element deletion (del1-PAI-pCAT) or very-low-density lipoprotein/fatty acid response element deletion (del2-PAI-pCAT) in the PAI-1 promoter were constructed and transiently transfected into HepG2 cells, respectively. Linoleic acid and fenofibrate were added to induce the transfected cells. The PAI-1 expression in mRNA and protein level was significantly induced by linoleic acid, but suppressed by fenofibrate. In the HepG2 cells transfected with PAI-pCAT plasmid, the PAI-1 transcription activity was significantly induced by linoleic acid, but suppressed by fenofibrate. Under transfection with del1-PAI-pCAT, both linoleic acid and fenofibrate increased the PAI-1 transcriptional activity; whereas in those cells transfected with del2-PAI-pCAT, fenofibrate significantly reduced PAI-1 transcriptional activity but no change was found with linoleic acid stimulation. Peroxisome proliferator-activated receptor alpha may be one of transcription factors playing a role in the upregulation of PAI-1 gene expression by linoleic acid in HepG2 cells. The inhibition of the nuclear factor-kappaB signaling pathway may be involved in the downregulation of PAI-1 gene expression by fenofibrate.
Ye
Ping
P
Department of Geriatric Cardiology, Chinese PLA General Hospital, Beijing, People's Republic of China. yeping@sina.com
He
Yan-Li
YL
Wang
Qiong
Q
Liu
Yong-Xue
YX
D045744:Cell Line, Tumor; D011345:Fenofibrate / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D005822:Genetic Vectors; D006801:Humans; D019787:Linoleic Acid / Q000494:pharmacology*; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000235:genetics; D017395:Plasminogen Activator Inhibitor 1 / Q000032:analysis / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection
D016328:NF-kappa B; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; D019787:Linoleic Acid; D011345:Fenofibrate