BFGF is lacking a secretion sequence and its release mechanism is not understood. Recently, we showed that shear stress induced bFGF release is mediated by integrin aVb3. Based on these findings we investigated whether matrix modulations by proteases contribute to the bFGF liberation.

Results: Aortic endothelial cells subjected to shear stress (16 dyn/cm2) exhibited increased elastase-like activity (3-fold vs. control, p<0.05) and released substancial amounts of bFGF (10- fold vs. control, p<0.05, n=6). Protease inhibition by aprotinin (1ug/ml)prevented shear stress induced bFGF liberation completely. Moreover, static cells treated with elastase showed increased bFGF cell surface staining which went along with a 1.8 fold higher bFGF release (p<0.05, n=6). As for shear stress, this protease-induced release could be prevented by inhibition of integrin aVb3. Further results indicate that HSP27 was phosphorylated upon elastase treatment integrin avb3 dependently. Phosphorylation of HSP27 was dependent on the p38 MAPK and phospho-Hsp27 co-precipitated with bFGF suggesting a function of HSP27 in bFGF release.

Conclusion: The release mechanism of bFGF is critically dependent on proteolytic matrix modulation via elastase and is subsequently regulated by specific cell-matrix interactions via the integrin aVb3. Moreover, Hsp27 phosphorylation may play a central role in the cellular transport machinery.