Heparan sulphate glycosaminoglycans derived from endothelial cells and smooth muscle cells differentially modulate fibroblast growth factor-2 biological activity through fibroblast growth factor receptor-1.
Fibroblast growth factor (FGF) signalling is involved in a wide range of important biological activities with differential effects in various cell types. The activity of FGF is modulated by heparin/heparan sulphate-like glycosaminoglycans (HSGAGs), found both in the extracellular matrix and on the cell surface. HSGAGs affect FGF signalling by interacting with both the growth factor and the FGF receptor (FGFR). In this study we sought to investigate whether HSGAGs at the cell surface of bovine aortic endothelial cells (BAEC) and smooth muscle cells (SMC) can differentially modulate FGF signalling in these cell types and modulate their differential response to FGF. We find that SMC and BAEC express the same FGFR isoforms and bind FGF2 with equal affinity at the cell surface, yet FGF has a markedly higher proliferative effect on SMC than on BAEC. Isolated HSGAGs from these two cell types were found to elicit distinct patterns of proliferation in chlorate-treated cells. Furthermore, examination of focal sequences reveals that HSGAGs from SMC, but not those from BAEC, retain the sulphation pattern necessary to induce FGF2 activity. As such, the differences in FGF2-mediated proliferation can be explained by the distinct cell surface HSGAGs of the two cell types. We conclude that the focal sequences of cell surface HSGAGs from SMC and BAEC govern, at least in part, the differential activity of FGF2 on these two cell types.
Berry
David
D
Harvard Medical School, 160 Longwood Avenue, Boston, MA 02215, USA.
Shriver
Zachary
Z
Natke
Barbara
B
Kwan
Chi-Pong
CP
Venkataraman
Ganesh
G
Sasisekharan
Ram
R
D000818:Animals; D001011:Aorta; D001483:Base Sequence; D002417:Cattle; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D017931:DNA Primers; D004187:Disaccharides / Q000737:chemistry; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D016222:Fibroblast Growth Factor 2 / Q000493:pharmacokinetics / Q000494:pharmacology*; D006497:Heparan Sulfate / Q000737:chemistry / Q000502:physiology*; D007700:Kinetics; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D020033:Protein Isoforms / Q000235:genetics; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000502:physiology*; D051496:Receptor, Fibroblast Growth Factor, Type 1; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics / Q000502:physiology*; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction
D017931:DNA Primers; D004187:Disaccharides; D016222:Fibroblast Growth Factor 2; D006497:Heparan Sulfate; D020033:Protein Isoforms; D020794:Receptor Protein-Tyrosine Kinases; D051496:Receptor, Fibroblast Growth Factor, Type 1; D017468:Receptors, Fibroblast Growth Factor; D011994:Recombinant Proteins