Basic fibroblast growth factor is released from endothelial extracellular matrix in a biologically active form

Area of Science:

• Cell Biology
• Biochemistry
• Extracellular Matrix Research

Background:

• Basic fibroblast growth factor (bFGF) is a key signaling molecule involved in cell growth and differentiation.
• The extracellular matrix (ECM) plays a crucial role in regulating growth factor availability and activity.
• Endothelial cells possess unique ECM interactions that influence cellular processes.

Purpose of the Study:

• To investigate the binding and release mechanisms of bFGF to the ECM of endothelial cells.
• To determine the biological activity of ECM-bound and released bFGF.
• To explore the role of heparin-like molecules and enzymes in bFGF-ECM interactions.

Main Methods:

• Utilized transformed fetal bovine aortic endothelial GM 7373 cells.
• Assessed bFGF binding to ECM using competition assays with heparin and heparan sulfate.
• Investigated ECM-bound bFGF release via enzymatic treatment (heparinase, heparatinase) and salt washes (2 M NaCl).
• Measured biological activity of released bFGF by assessing cell-associated plasminogen activator activity and cell proliferation.

Main Results:

• bFGF binds to heparin-like molecules within the endothelial cell ECM.
• ECM-bound bFGF is released in a biologically active form, stimulating cell proliferation and plasminogen activator activity.
• Heparinase or heparatinase treatment releases ECM-bound bFGF.
• Soluble heparin and heparan sulfate reduce bFGF release, potentially by inhibiting ECM-mobilizing enzymes.

Conclusions:

• Endothelial cell ECM serves as a reservoir for biologically active bFGF.
• The release of ECM-bound bFGF is mediated by specific enzymes and can be modulated by heparin and heparan sulfate.
• These findings highlight the importance of ECM-bFGF interactions in regulating endothelial cell function and signaling.