Urokinase‐type plasminogen activator mediates basic fibroblast growth factor‐induced bovine endothelial cell migration independent of its proteolytic activity

Lale E. Odekon, Yasufumi Sato, Daniel B. Rifkin

Research output: Contribution to journalArticlepeer-review

169 Citations (Scopus)

Abstract

The dependence of urokinase‐type plasminogen activator (uPA) induction on endogenous basic fibroblast growth factor (bFGF) activity during endothelial cell migration was investigated utilizing a combination of wounded endothelial cell monolayers and substrate overlay techniques. Purified polyclonal rabbit immunoglobulin G (IgG) against bFGF blocked the appearance of uPA‐dependent lytic activity normally observed at the edge of a wounded bovine aortic endothelial (BAE) cell monolayer. Additionally, the migration of cells into the denuded area was inhibited 30–50% by antibodies either to bFGF or to bovine uPA. Incubation of wounded monolayers with either purified bovine uPA or agents able to induce PA activity, such as phorbol myristate acetate (PMA), vanadate, or bFGF, resulted in enhanced migration of cells (28–50%). Anti‐bovine uPA IgG blocked a significant fraction (25%) of BAE cell migration induced by exposure to exogenous bFGF. The role of uPA in migration of wounded BAE cells was not dependent on plasmin generation. Furthermore, the amino terminal fragment (ATF) of human recombinant (hr) uPA, which is enzymatically inactive, stimulated BAE cell movement (36%) as well as intact uPA. ATF of hr uPA also stimulated endothelial cell movement in the presence of anti‐bFGF IgG. These results suggest that BAE cell migration from the edge of a wounded monolayer is dependent upon local increases of uPA mediated by endogenous bFGF. Moreover, the data support the conclusion that migration is stimulated via a signalling mechanism dependent upon occupancy of the uPA receptor but independent of uPA‐mediated proteolysis.

Original languageEnglish
Pages (from-to)258-263
Number of pages6
JournalJournal of Cellular Physiology
Volume150
Issue number2
DOIs
Publication statusPublished - 1992 Feb
Externally publishedYes

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

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