Apoptotic effect of cleaved high molecular weight kininogen is regulated by extracellular matrix proteins

Yan Lin Guo, Shujie Wang, Dian J. Cao, Robert W. Colman

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

We previously reported that cleaved high molecular weight kininogen (HKa) and its domain 5 (D5) inhibit critical steps required for angiogenesis and in vivo neovascularization (Colman et al. [2000]: Blood 95:543-550). We have further shown that D5 is able to induce apoptosis of endothelial cells, which may represent a critical part of the antiangiogenic activity of HKa and D5 (Guo et al. [2001]: Arterioscler Thromb Vasc Biol 21:1427-1433). In this study, we demonstrate that HKa- and D5-induced apoptosis is closely correlated with their anti-adhesive effect. An important new finding is that the apoptotic activity of HKa and D5 is highly regulated by their interactions with different extracellular matrix (ECM) proteins. H Ka inhibited cell adhesion to vitronectin (Vn, 90%) and gelatin (Gel) (40%), but it had no apparent effect on cell adhesion to fibronectin (Fn). D5 showed a similar pattern on cell adhesion but was less potent than HKa. HKa induced apoptosis of endothelial cells grown on Vn and Gel but not cells grown on Fn which closely parallels with its antiadhesive potency. Further results revealed that the anti-adhesive effect and the apoptotic effect of HKa are associated with its ability to inhibit phosphorylation of focal adhesion kinase (FAK) and paxillin, two important signal molecules required for cell adhesion and cell viability. We conclude that the anti-adhesive activity of HKa and D5 is responsible for their apoptotic effect and that Vn is likely an ECM component that mediates the effect of HKa and D5.

Original languageEnglish (US)
Pages (from-to)622-632
Number of pages11
JournalJournal of Cellular Biochemistry
Volume89
Issue number3
DOIs
StatePublished - Jun 1 2003

Keywords

  • Angiogenesis
  • Apoptosis
  • Cell adhesion
  • Endothelial cells
  • Focal adhesion kinase

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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