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

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.