title: Heparan sulfate interacting protein (HIP/L29) negatively regulates growth responses to basic fibroblast growth factor in gingival fibroblasts.
abstract: Basic fibroblast growth factor (bFGF) modulates gingival growth, and its release from heparan sulfate (HS) in the extracellular matrix (ECM) governs local tissue bioavailability. We identified a heparin/HS interacting protein (HIP/L29) that recognizes specific HS sequences. We hypothesize that HIP/L29, by modulating the interactions of bFGF with HS chains on proteoglycans, could regulate bFGF bioavailability. To investigate interactions between bFGF and HIP/L29, we isolated and cultured fibroblasts from normal gingiva and overgrown gingiva from patients on cyclosporine (CSA). bFGF significantly stimulated gingival fibroblast proliferation with or without heparin. Recombinant human HIP/L29 dramatically decreased bFGF-induced proliferation, but did not alter responses to insulin-like growth factor-1 (IGF-1). Analysis of mitogen-activated protein kinase (MAPK) phosphorylation patterns showed that bFGF stimulation of p44 (Erk-1), but not p42 (Erk-2), also was inhibited by HIP/L29 in a dose-dependent manner. Together, these results support our hypothesis that HIP/L29 modulates the bioavailability and action of bFGF.
authors.affiliation: Department of Biological Sciences, University of Delaware, Newark 19716, USA.
authors.forename: T-V
authors.initials: TV
authors.lastname: Ta
authors.forename: D
authors.initials: D
authors.lastname: Baraniak
authors.forename: J
authors.initials: J
authors.lastname: Julian
authors.forename: J
authors.initials: J
authors.lastname: Korostoff
authors.forename: D D
authors.initials: DD
authors.lastname: Carson
authors.forename: M C
authors.initials: MC
authors.lastname: Farach-Carson
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001682:Biological Availability; D002417:Cattle; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004789:Enzyme Activation; D016222:Fibroblast Growth Factor 2 / Q000037:antagonists & inhibitors / Q000502:physiology*; D005347:Fibroblasts / Q000166:cytology; D005881:Gingiva / Q000166:cytology / Q000187:drug effects / Q000254:growth & development*; D005885:Gingival Hyperplasia / Q000139:chemically induced / Q000503:physiopathology; D006133:Growth Substances / Q000494:pharmacology / Q000502:physiology; D006801:Humans; D020935:MAP Kinase Signaling System; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010766:Phosphorylation; D011994:Recombinant Proteins / Q000494:pharmacology; D012269:Ribosomal Proteins / Q000494:pharmacology / Q000502:physiology*; D018709:Statistics, Nonparametric
chemical_list: D006133:Growth Substances; D011994:Recombinant Proteins; D012269:Ribosomal Proteins; C035078:ribosomal protein L29; D016222:Fibroblast Growth Factor 2; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases