Plasminogen activator inhibitor-1 is induced in migrating endothelial cells.
It has been proposed that a finely tuned protease-anti-protease equilibrium must be maintained during processes of cell migration in order to limit extracellular proteolysis to the close proximity of the cell surface, and thereby to prevent excessive extracellular matrix degradation. We have previously shown that urokinase-type plasminogen activator (u-PA) activity is induced in microvascular endothelial cells migrating from the edges of a wounded monolayer in vitro (Pepper et al., J. Cell Biol., 105:2535-2541, 1987). By Northern analysis, we now demonstrate that plasminogen activator inhibitor 1 (PAI-1) mRNA is increased in multiple-wounded monolayers of bovine microvascular (BME) or aortic (BAE) endothelial cells, with a maximal 7- and 9-fold increase 4 h after wounding, respectively. By in situ hybridization, we demonstrate that the increase in PAI-1 mRNA is localized to cells at the edge of a wounded BME or BAE cell monolayer. The increase in PAI-1 mRNA observed in BME cells is independent of cell division and is inhibited by antibodies to basic fibroblast growth factor (bFGF), suggesting that PAI-1 induction in migrating cells is mediated by the autocrine activity of bFGF. Taken together with our previous observations on the induction of u-PA, these results support the hypothesis that the proteolytic balance in the pericellular environment of migrating cells is regulated through the concomitant production of proteases and protease inhibitors.
Pepper
M S
MS
Institute of Histology and Embryology, University of Geneva Medical Center, Switzerland.
Sappino
A P
AP
Montesano
R
R
Orci
L
L
Vassalli
J D
JD
D000818:Animals; D015152:Blotting, Northern; D002417:Cattle; D002452:Cell Count; D002465:Cell Movement / Q000502:physiology; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology* / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000276:immunology / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology*; D006023:Glycoproteins / Q000235:genetics; D008666:Metalloendopeptidases / Q000235:genetics; D010957:Plasmids / Q000235:genetics; D015849:Plasminogen Inactivators / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D019714:Tissue Inhibitor of Metalloproteinases
D006023:Glycoproteins; D015849:Plasminogen Inactivators; D012333:RNA, Messenger; D019714:Tissue Inhibitor of Metalloproteinases; D016222:Fibroblast Growth Factor 2; D008666:Metalloendopeptidases