title: Impact of fibroblast growth factor-binding protein-1 expression on angiogenesis and wound healing.
abstract: Fibroblast growth factors (FGFs) participate in embryonic development, in maintenance of tissue homeostasis in the adult, and in various diseases. FGF-binding proteins (FGFBP) are secreted proteins that chaperone FGFs stored in the extracellular matrix to their receptor, and can thus modulate FGF signaling. FGFBP1 (alias BP1, FGF-BP1, or HBp17) expression is required for embryonic survival, can modulate FGF-dependent vascular permeability in embryos, and is an angiogenic switch in human cancers. To determine the function of BP1 in vivo, we generated tetracycline-regulated conditional BP1 transgenic mice. BP1-expressing adult mice are viable, fertile, and phenotypically indistinguishable from their littermates. Induction of BP1 expression increased mouse primary fibroblast motility in vitro, increased angiogenic sprouting into subcutaneous matrigel plugs in animals and accelerated the healing of excisional skin wounds. FGF-receptor kinase inhibitors blocked these effects. Healing skin wounds showed increased macrophage invasion as well as cell proliferation after BP1 expression. Also, BP1 expression increased angiogenesis during the healing of skin wounds as well as after ischemic injury to hindlimb skeletal muscles. We conclude that BP1 can enhance FGF effects that are required for the healing and repair of injured tissues in adult animals.
authors.affiliation: Lombardi Cancer Center, Georgetown University, Washington, DC, USA.
authors.forename: Elena
authors.initials: E
authors.lastname: Tassi
authors.forename: Kevin
authors.initials: K
authors.lastname: McDonnell
authors.forename: Krissa A
authors.initials: KA
authors.lastname: Gibby
authors.forename: Jason U
authors.initials: JU
authors.lastname: Tilan
authors.forename: Sung E
authors.initials: SE
authors.lastname: Kim
authors.forename: David P
authors.initials: DP
authors.lastname: Kodack
authors.forename: Marcel O
authors.initials: MO
authors.lastname: Schmidt
authors.forename: Ghada M
authors.initials: GM
authors.lastname: Sharif
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Wilcox
authors.forename: William J
authors.initials: WJ
authors.lastname: Welch
authors.forename: G Ian
authors.initials: GI
authors.lastname: Gallicano
authors.forename: Michael D
authors.initials: MD
authors.lastname: Johnson
authors.forename: Anna T
authors.initials: AT
authors.lastname: Riegel
authors.forename: Anton
authors.initials: A
authors.lastname: Wellstein
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002465:Cell Movement; D002478:Cells, Cultured; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D005347:Fibroblasts / Q000378:metabolism*; D006614:Hindlimb / Q000098:blood supply; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; D007511:Ischemia / Q000378:metabolism / Q000503:physiopathology; D008264:Macrophages / Q000502:physiology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D018919:Neovascularization, Physiologic / Q000502:physiology*; D011994:Recombinant Proteins; D012867:Skin / Q000293:injuries; D019076:Transgenes / Q000502:physiology; D014945:Wound Healing / Q000502:physiology*
chemical_list: D002352:Carrier Proteins; C489453:Fgfbp1 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; D011994:Recombinant Proteins; D016222:Fibroblast Growth Factor 2