Release of bFGF from endotelial cells is mediated by protease induced HSP27 phosphorylation via p38-MAPK pathway

Mogensen, Christina Klarskov (2006): Release of bFGF from endotelial cells is mediated by protease induced HSP27 phosphorylation via p38-MAPK pathway. Dissertation, LMU München: Fakultät für Chemie und Pharmazie

Abstract

Introduction: Factors and other stimuli that lead to the release of basic fibroblast growth factor (bFGF) from endothelial cells may be essential for physiological processes such as development and angiogenesis. The release mechanisms are somewhat obscure and it has previously been shown that in the case of shear stress induced bFGF release cell matrix interaction is critically mediating that bFGF release (Gloe et al., 2002). Considering the potential role of proteolytically modified extra-cellular matrix components in the induction of cellular signaling cascades, the aim of the present study was to investigate whether elastase activity contributes to the release of bFGF from endothelial cells. Methods and results: Treatment of porcine aortic endothelial cells with elastase led to a release of bFGF in a concentration-dependent manner. This release was strictly regulated and could be reduced by inhibition of integrin v3. Moreover, bFGF was translocated towards the cell membrane after elastase treatment as well as shear stress exposure, in close proximity to HSP27. Furthermore, elastase treatment led to a p38 MAP Kinase dependent HSP27 phosphorylation and this phospho-HSP27 could be shown to co-precipitate with bFGF. Conclusion: We conclude that elastolytic activities activated by shear stress are involved in the active release of bFGF from endothelial cells and that phosphorylation of HSP27 is prerequisite for this release mechanism. The results may reflect the critical role of proteases in the initial process of angiogenesis induction.

• Dokumententyp: Dissertationen (Dissertation, LMU München)
• Keywords: bFGF, elastase, HSP27, integrin, shear stress
• Themengebiete: 500 Naturwissenschaften und Mathematik ; 500 Naturwissenschaften und Mathematik > 540 Chemie
• Fakultäten: Fakultät für Chemie und Pharmazie
• Sprache der Hochschulschrift: Englisch
• Datum der mündlichen Prüfung: 30. Januar 2006
• 1. Bericht­erstatter:in: Pohl, Ulrich