title: Fibroblast Growth Factor Receptor-2 Contributes to the Basic Fibroblast Growth Factor-Induced Neuronal Differentiation in Canine Bone Marrow Stromal Cells via Phosphoinositide 3-Kinase/Akt Signaling Pathway.
abstract: Bone marrow stromal cells (BMSCs) are considered as candidates for regenerative therapy and a useful model for studying neuronal differentiation. The role of basic fibroblast growth factor (bFGF) in neuronal differentiation has been previously studied; however, the signaling pathway involved in this process remains poorly understood. In this study, we investigated the signaling pathway in the bFGF-induced neuronal differentiation of canine BMSCs. bFGF induced the mRNA expression of the neuron marker, microtubule associated protein-2 (MAP2) and the neuron-like morphological change in canine BMSCs. In the presence of inhibitors of fibroblast growth factor receptors (FGFR), phosphatidylinositol 3-kinase (PI3K) and Akt, i.e., SU5402, LY294002, and MK2206, respectively, bFGF failed to induce the MAP2 mRNA expression and the neuron-like morphological change. bFGF induced Akt phosphorylation, but it was attenuated by the FGFR inhibitor SU5402 and the PI3K inhibitor LY294002. In canine BMSCs, expression of FGFR-1 and FGFR-2 was confirmed, but only FGFR-2 activation was detected by cross-linking and immunoprecipitation analysis. Small interfering RNA-mediated knockdown of FGFR-2 in canine BMSCs resulted in the attenuation of bFGF-induced Akt phosphorylation. These results suggest that the FGFR-2/PI3K/Akt signaling pathway is involved in the bFGF-induced neuronal differentiation of canine BMSCs.
authors.affiliation: Laboratory of Veterinary Surgery, Department of Veterinary Medicine, College of Bioresource Sciences, Nihon University, Kameino, Fujisawa, Kanagawa, Japan; Laboratory of Veterinary Biochemistry, Department of Veterinary Medicine, College of Bioresource Sciences, Nihon University, Kameino, Fujisawa, Kanagawa, Japan.
authors.forename: Rei
authors.initials: R
authors.lastname: Nakano
authors.affiliation: Laboratory of Veterinary Surgery, Department of Veterinary Medicine, College of Bioresource Sciences, Nihon University, Kameino, Fujisawa, Kanagawa, Japan.
authors.forename: Kazuya
authors.initials: K
authors.lastname: Edamura
authors.affiliation: Laboratory of Veterinary Radiology, Department of Veterinary Medicine, College of Bioresource Sciences, Nihon University, Kameino, Fujisawa, Kanagawa, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Nakayama
authors.affiliation: Laboratory of Veterinary Biochemistry, Department of Veterinary Medicine, College of Bioresource Sciences, Nihon University, Kameino, Fujisawa, Kanagawa, Japan.
authors.forename: Takanori
authors.initials: T
authors.lastname: Narita
authors.affiliation: Laboratory of Veterinary Biochemistry, Department of Veterinary Medicine, College of Bioresource Sciences, Nihon University, Kameino, Fujisawa, Kanagawa, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Okabayashi
authors.affiliation: Laboratory of Veterinary Biochemistry, Department of Veterinary Medicine, College of Bioresource Sciences, Nihon University, Kameino, Fujisawa, Kanagawa, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sugiya
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D004285:Dogs; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects*; D008869:Microtubule-Associated Proteins / Q000235:genetics; D009474:Neurons / Q000166:cytology* / Q000187:drug effects; D051058:Oncogene Protein v-akt / Q000235:genetics / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D008869:Microtubule-Associated Proteins; D016222:Fibroblast Growth Factor 2; D019869:Phosphatidylinositol 3-Kinases; D051497:Receptor, Fibroblast Growth Factor, Type 2; D051058:Oncogene Protein v-akt