title: Role of urokinase and its receptor in basal and stimulated colonic epithelial cell migration in vitro.
abstract: BACKGROUND
  Migration of colonic epithelial cells is important for mucosal repair following injury. The urokinase (u-PA) system regulates migration in other cell types.
  
  
  OBJECTIVE
  To examine the role of u-PA and its receptor (u-PAR) in colonic epithelial cell migration.
  
  
  METHODS
  Migration was assessed over 24 hours in circular wounds made in confluent monolayers of LIM1215 and Caco-2 human colon cancer cells. The function of u-PA and u-PAR was ablated with antisense oligonucleotides to block expression, with synthetic u-PA peptides to block interaction, and with aprotinin to block u-PA mediated proteolysis.
  
  
  RESULTS
  Migration was stimulated two to threefold by exogenous u-PA, an effect dependent on u-PAR binding but independent of u-PA mediated mitogenesis and proteolysis. Expression of u-PA and u-PAR was inhibited by 80% by the appropriate antisense oligonucleotide. Basal migration and the motogenic effects of butyrate, epidermal growth factor, and phorbol-12-myristate-13-acetate were suppressed by the u-PAR antisense oligonucleotide (40-60%) but were at best minimally affected following inhibition of u-PA expression and binding.
  
  
  CONCLUSIONS
  In an in vitro model of wounded colonic epithelium, u-PAR promotes cell migration through mechanisms that are not exclusively dependent on u-PA binding. Therefore, u-PA and u-PAR may contribute to colonic mucosal repair in vivo.
authors.affiliation: Department of Medicine, University of Melbourne, Royal Melbourne Hospital, Victoria 3050, Australia.
authors.forename: A J
authors.initials: AJ
authors.lastname: Wilson
authors.forename: P R
authors.initials: PR
authors.lastname: Gibson
mesh_terms: D002087:Butyrates / Q000494:pharmacology; D018938:Caco-2 Cells; D002455:Cell Division / Q000502:physiology; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D003106:Colon / Q000201:enzymology* / Q000293:injuries / Q000473:pathology; D004815:Epidermal Growth Factor / Q000494:pharmacology; D004847:Epithelial Cells / Q000502:physiology*; D006801:Humans; D016376:Oligonucleotides, Antisense / Q000235:genetics; D011956:Receptors, Cell Surface / Q000235:genetics / Q000502:physiology*; D055293:Receptors, Urokinase Plasminogen Activator; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*
chemical_list: D002087:Butyrates; D016376:Oligonucleotides, Antisense; C524898:PLAUR protein, human; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D004815:Epidermal Growth Factor; D014568:Urokinase-Type Plasminogen Activator; D013755:Tetradecanoylphorbol Acetate