PMID- 23530859 OWN - NLM STAT- MEDLINE DCOM- 20140210 LR - 20211021 IS - 1937-335X (Electronic) IS - 1937-3341 (Print) IS - 1937-3341 (Linking) VI - 19 IP - 15-16 DP - 2013 Aug TI - Nerve growth factor, brain-derived neurotrophic factor, neurotrophin-3 and glial-derived neurotrophic factor enhance angiogenesis in a tissue-engineered in vitro model. PG - 1655-64 LID - 10.1089/ten.tea.2012.0745 [doi] AB - 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, GFRalpha-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. FAU - Blais, Mathieu AU - Blais M AD - Departement de Chirurgie, Faculte de Medecine, Centre LOEX de l'Universite Laval, Centre de recherche du CHU de Quebec, Universite Laval, Quebec, Canada. FAU - Levesque, Philippe AU - Levesque P FAU - Bellenfant, Sabrina AU - Bellenfant S FAU - Berthod, Francois AU - Berthod F LA - eng GR - MOP-106429/Canadian Institutes of Health Research/Canada PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130326 PL - United States TA - Tissue Eng Part A JT - Tissue engineering. Part A JID - 101466659 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Glial Cell Line-Derived Neurotrophic Factor) RN - 0 (Nerve Growth Factors) RN - 0 (Neurotrophin 3) SB - IM MH - Brain-Derived Neurotrophic Factor/*pharmacology MH - Cells, Cultured MH - Enzyme-Linked Immunosorbent Assay MH - Fibroblasts MH - Fluorescent Antibody Technique, Indirect MH - Glial Cell Line-Derived Neurotrophic Factor/*pharmacology MH - Humans MH - Neovascularization, Physiologic/*drug effects MH - Nerve Growth Factors/*pharmacology MH - Neurotrophin 3/*pharmacology MH - Tissue Engineering PMC - PMC3700174 EDAT- 2013/03/28 06:00 MHDA- 2014/02/11 06:00 PMCR- 2014/08/01 CRDT- 2013/03/28 06:00 PHST- 2013/03/28 06:00 [entrez] PHST- 2013/03/28 06:00 [pubmed] PHST- 2014/02/11 06:00 [medline] PHST- 2014/08/01 00:00 [pmc-release] AID - 10.1089/ten.tea.2012.0745 [pii] AID - 10.1089/ten.tea.2012.0745 [doi] PST - ppublish SO - Tissue Eng Part A. 2013 Aug;19(15-16):1655-64. doi: 10.1089/ten.tea.2012.0745. Epub 2013 Mar 26.