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Epithelial proliferation and imaging
Role of urokinase and its receptor in basal and stimulated colonic epithelial cell migration in vitro
  1. A J Wilson,
  2. P R Gibson
  1. Department of Medicine, University of Melbourne, Royal Melbourne Hospital, Victoria 3050, Australia
  1. Professor Peter Gibson. Email: p.gibson{at}medicine.unimelb.edu.au

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.

AIM 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.

  • colon
  • migration
  • urokinase
  • urokinase receptor
  • epidermal growth factor
  • butyrate
  • protein kinase C

  • Abbreviations used in this paper

    EGF
    epidermal growth factor
    MD
    migration differential
    PKC
    protein kinase C
    ON
    oligonucleotide
    PMA
    phorbol-12-myristate-13-acetate
    u-PA
    urokinase-type plasminogen activator
    u-PAR
    u-PA receptor
    LDH
    lactate dehydrogenase
    PKC
    protein kinase C

    • https://doi.org/10.1136/gut.47.1.105

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    • Abbreviations used in this paper

      EGF
      epidermal growth factor
      MD
      migration differential
      PKC
      protein kinase C
      ON
      oligonucleotide
      PMA
      phorbol-12-myristate-13-acetate
      u-PA
      urokinase-type plasminogen activator
      u-PAR
      u-PA receptor
      LDH
      lactate dehydrogenase
      PKC
      protein kinase C
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