Lysophosphatidylcholine induces tPA gene expression through CRE-dependent mechanism.
Lysophosphatidylcholine (lysoPC) is implicated in the development of atherosclerosis and certain autoimmune diseases, and is reported to induce tissue-type plasminogen activator (tPA) at the protein level in endothelial cells. This study was designed to investigate the effect of lysoPC on tPA gene expression and the underlying molecular mechanisms in cultured endothelial cells. LysoPC transiently induced the mRNA expression of tPA in endothelial cells. LysoPC also induced the mRNA expression of urokinase-type plasminogen activator (uPA), uPA receptor, and plasminogen activator inhibitor-1, but the kinetics were different from that of tPA. Promoter analysis revealed that the cyclic AMP-responsive element of the tPA gene (tPACRE) is required for lysoPC-induced tPA expression. Furthermore, an electrophoresis mobility shift assay showed that lysoPC increased the binding activity of CRE binding protein to tPACRE. These results indicated that lysoPC transcriptionally upregulated the gene expression of tPA in endothelial cells, at least in part, via tPACRE activation.
Sheikh
Abdullah Md
AM
Department of Laboratory Medicine, Shimane University School of Medicine, Izumo, Japan.
Ochi
Hiroshi
H
Masuda
Junichi
J
D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D002633:Chemotaxis; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D004789:Enzyme Activation; D004797:Enzyme-Linked Immunosorbent Assay; D017353:Gene Deletion; D005786:Gene Expression Regulation; D006801:Humans; D007700:Kinetics; D008156:Luciferases / Q000378:metabolism; D008244:Lysophosphatidylcholines / Q000494:pharmacology*; D008957:Models, Genetic; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012333:RNA, Messenger / Q000378:metabolism; D020218:Response Elements; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000378:metabolism*; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D015854:Up-Regulation; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics / Q000378:metabolism*
D008244:Lysophosphatidylcholines; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; D008156:Luciferases; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator