Basic fibroblast growth factor binds to subendothelial extracellular matrix and is released by heparitinase and heparin-like molecules

Journal Article · Tue Feb 21 00:00:00 EST 1989 · Biochemistry; (USA)

DOI:https://doi.org/10.1021/bi00430a047· OSTI ID:5546963

Bashkin, P; Doctrow, S; Klagsbrun, M; Svahn, C M; Folkman, J; Vlodavsky, I ^[1]

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1. Hadassah Univ. Hospital, Jerusalem (Israel)

Basic fibroblast growth factor (bFGF) exhibits specific binding to the extracellular matrix (ECM) produced by cultured endothelial cells. Binding was saturable as a function both of time and of concentration of {sup 125}I-bFGF. Scatchard analysis of FGF binding revealed the presence of about 1.5 x 10{sup 12} binding sites/mm{sup 2} ECM with an apparent k{sub D} of 610 nM. FGF binds to heparan sulfate (HS) in ECM as evidenced by (i) inhibition of binding in the presence of heparin or HS at 0.1-1 {mu}g/mL, but not by chondroitin sulfate, keratan sulfate, or hyaluronic acid at 10 {mu}g/mL, (ii) lack of binding to ECM pretreated with heparitinase, but not with chondroitinase ABC, and (iii) rapid release of up to 90% of ECM-bound FGF by exposure to heparin, HS, or heparitinase, but not to chondroitin sulfate, keratan sulfate, hyaluronic acid, or chondroitinase ABC. Oligosaccharides derived from depolymerized heparin, and as small as the tetrasaccharide, released the ECM-bound FGF, but there was little or no release of FGF by modified nonanticoagulant heparins such as totally desulfated heparin, N-desulfated heparin, and N-acetylated heparin. FGF released from ECM was biologically active, as indicated by its stimulation of cell proliferation and DNA synthesis in vascular endothelial cells and 3T3 fibroblasts. Similar results were obtained in studies on release of endogenous FGF-like mitogenic activity from Descement's membranes of bovine corneas. It is suggested that ECM storage and release of bFGF provide a novel mechanism for regulation of capillary blood vessel growth. Whereas ECM-bound FGF may be prevented from acting on endothelial cells, its displacement by heparin-like molecules and/or HS-degrading enzymes may elicit a neovascular response.

• OSTI ID: 5546963
• Journal Information: Biochemistry; (USA), Vol. 28:4; ISSN 0006-2960
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
FIBROBLASTS
CELL PROLIFERATION
GROWTH FACTORS
BIOCHEMICAL REACTION KINETICS
DOSE-RESPONSE RELATIONSHIPS
ENDOTHELIUM
HEPARIN
IODINATION
IODINE 125
MOLECULAR WEIGHT
THYMIDINE
TRITIUM COMPOUNDS
AMINES
ANIMAL CELLS
ANIMAL TISSUES
ANTICOAGULANTS
AZINES
BETA DECAY RADIOISOTOPES
BODY
CARBOHYDRATES
CHEMICAL REACTIONS
CONNECTIVE TISSUE CELLS
DAYS LIVING RADIOISOTOPES
DRUGS
ELECTRON CAPTURE RADIOISOTOPES
HALOGENATION
HEMATOLOGIC AGENTS
HETEROCYCLIC COMPOUNDS
HYDROGEN COMPOUNDS
INTERMEDIATE MASS NUCLEI
IODINE ISOTOPES
ISOTOPES
KINETICS
MITOGENS
MUCOPOLYSACCHARIDES
NUCLEI
NUCLEOSIDES
NUCLEOTIDES
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC SULFUR COMPOUNDS
POLYSACCHARIDES
PROTEINS
PYRIMIDINES
RADIOISOTOPES
REACTION KINETICS
RIBOSIDES
SACCHARIDES
SOMATIC CELLS
TISSUES
550201* - Biochemistry- Tracer Techniques