title: Nerve growth factor, brain-derived neurotrophic factor, neurotrophin-3 and glial-derived neurotrophic factor enhance angiogenesis in a tissue-engineered in vitro model.
abstract: Skin is a major source of secretion of the neurotrophic factors nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and glial-derived neurotrophic factor (GDNF) controlling cutaneous sensory innervation. Beside their neuronal contribution, we hypothesized that neurotrophic factors also modulate the cutaneous microvascular network. First, we showed that NGF, BDNF, NT-3, and GDNF were all expressed in the epidermis, while only NGF and NT-3 were expressed by cultured fibroblasts, and BDNF by human endothelial cells. We demonstrated that these peptides are highly potent angiogenic factors using a human tissue-engineered angiogenesis model. A 40% to 80% increase in the number of capillary-like tubes was observed after the addition of 10 ng/mL of NGF, 0.1 ng/mL of BDNF, 15 ng/mL of NT-3, and 50 ng/mL of GDNF. This is the first characterization of the direct angiogenic effect of NT-3 and GDNF. This angiogenic effect was mediated directly through binding with the neurotrophic factor receptors tropomyosin-receptor kinase A (TrkA), TrkB, GFRα-1 and c-ret that were all expressed by human endothelial cells, while this effect was blocked by addition of the Trk inhibitor K252a. Thus, if NGF, BDNF, NT-3, and GDNF may only moderately regulate the microvascular network in normal skin, they might have the potential to greatly increase angiogenesis in pathological situations.
authors.affiliation: Département de Chirurgie, Faculté de Médecine, Centre LOEX de l'Université Laval, Centre de recherche du CHU de Québec, Université Laval, Québec, Canada.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Blais
authors.forename: Philippe
authors.initials: P
authors.lastname: Lévesque
authors.forename: Sabrina
authors.initials: S
authors.lastname: Bellenfant
authors.forename: François
authors.initials: F
authors.lastname: Berthod
mesh_terms: D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology*; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005347:Fibroblasts; D019084:Fluorescent Antibody Technique, Indirect; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000494:pharmacology*; D006801:Humans; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D009414:Nerve Growth Factors / Q000494:pharmacology*; D020933:Neurotrophin 3 / Q000494:pharmacology*; D023822:Tissue Engineering
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D020933:Neurotrophin 3