Fibrinogen and fibrin protect fibroblast growth factor-2 from proteolytic degradation.
We have recently reported that fibrinogen and fibrin bind to fibroblast growth factor-2 (FGF-2) and potentiate its ability to stimulate proliferation of endothelial cells. In the present report, we have investigated the potential of fibrinogen and fibrin to protect FGF-2 from proteolytic degradation. FGF-2 was incubated with trypsin or chymotrypsin in the presence or absence of fibrinogen or fibrin and proteolysis of FGF-2 was assessed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and Western blotting. In the absence of fibrinogen there was progressive tryptic degradation of FGF-2, but in the presence of fibrinogen, FGF-2 was completely protected from trypsin with no evidence of degradation. The degree of protection was maximum at a molar ratio of FGF-2 to fibrinogen 1:2. Fibrinogen afforded similar protection from degradation by chymotrypsin. Polymerized fibrin provided partial protection of FGF-2 from tryptic degradation, with intact FGF-2 present for up to 360 min. Fibrin provided nearly complete protection from chymotrypsin. These observations indicate that binding of FGF-2 to fibrinogen or fibrin provides protection from proteolytic degradation, and this may modulate its cell proliferative activity.
Sahni
A
A
Department of Medicine, University of Rochester School of Medicine and Dentistry, NY, USA.
Baker
C A
CA
Sporn
L A
LA
Francis
C W
CW
D001704:Biopolymers; D015153:Blotting, Western; D002918:Chymotrypsin / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D005337:Fibrin / Q000737:chemistry / Q000494:pharmacology*; D005340:Fibrinogen / Q000494:pharmacology; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D006801:Humans; D006868:Hydrolysis / Q000187:drug effects; D009994:Osmolar Concentration; D011485:Protein Binding; D011994:Recombinant Proteins / Q000378:metabolism; D014357:Trypsin / Q000378:metabolism
D001704:Biopolymers; D011994:Recombinant Proteins; D016222:Fibroblast Growth Factor 2; D005337:Fibrin; D005340:Fibrinogen; D002918:Chymotrypsin; D014357:Trypsin