Article Text
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
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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