title: Localization of regulatory elements mediating constitutive and cytokine-stimulated plasminogen gene expression.
abstract: The activity of plasmin, the major enzyme responsible for dissolving fibrin clots, is regulated by plasminogen activators, plasminogen activator inhibitors, alpha(2)-antiplasmin, and inflammatory mediators. Recent studies suggest that plasmin activity can be regulated also at the level of plasminogen gene expression. In this study, we characterized the murine plasminogen promoter and 5'-flanking region. The major transcription start site was identified at -83 bp relative to the ATG translational initiation codon. A series of 5'-flanking sequences up to 2400 bp upstream of the transcription initiation site were fused to the luciferase reporter gene and transfected into hepatocytic cells. A 106-bp 5'-flanking region of the murine plasminogen gene demonstrated sufficient functional promoter activity in plasminogen-expressing cells. IL-6 treatment stimulated luciferase activity driven by the 5'-flanking region and an intact consensus IL-6-responsive element at -791, was required for maximal stimulation by this cytokine. These results indicate the presence of regulatory elements in the 5'-flanking region of the murine plasminogen promoter that may regulate murine plasminogen gene expression and, hence, plasmin activity.
authors.affiliation: Department of Cell Biology, Division of Vascular Biology, Scripps Research Institute, La Jolla, California 92037, USA. fbannach@ucsd.edu
authors.forename: Felizabel Garcia
authors.initials: FG
authors.lastname: Bannach
authors.forename: Ana
authors.initials: A
authors.lastname: Gutierrez
authors.forename: Bruce J
authors.initials: BJ
authors.lastname: Fowler
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Bugge
authors.forename: Jay L
authors.initials: JL
authors.lastname: Degen
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Parmer
authors.forename: Lindsey A
authors.initials: LA
authors.lastname: Miles
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D005343:Fibrinolytic Agents / Q000378:metabolism; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D022781:Hepatocytes / Q000166:cytology; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D008156:Luciferases / Q000235:genetics; D051379:Mice; D008969:Molecular Sequence Data; D010958:Plasminogen / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D020218:Response Elements; D014157:Transcription Factors / Q000378:metabolism; D024363:Transcription Initiation Site; D014158:Transcription, Genetic
chemical_list: D005343:Fibrinolytic Agents; D015850:Interleukin-6; D014157:Transcription Factors; D010958:Plasminogen; D008156:Luciferases