PMID- 26523832
OWN - NLM
STAT- MEDLINE
DCOM- 20160620
LR  - 20181202
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 10
IP  - 11
DP  - 2015
TI  - 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.
PG  - e0141581
LID - 10.1371/journal.pone.0141581 [doi]
LID - e0141581
AB  - 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.
FAU - Nakano, Rei
AU  - Nakano R
AD  - 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.
FAU - Edamura, Kazuya
AU  - Edamura K
AD  - Laboratory of Veterinary Surgery, Department of Veterinary Medicine, College of 
      Bioresource Sciences, Nihon University, Kameino, Fujisawa, Kanagawa, Japan.
FAU - Nakayama, Tomohiro
AU  - Nakayama T
AD  - Laboratory of Veterinary Radiology, Department of Veterinary Medicine, College of 
      Bioresource Sciences, Nihon University, Kameino, Fujisawa, Kanagawa, Japan.
FAU - Narita, Takanori
AU  - Narita T
AD  - Laboratory of Veterinary Biochemistry, Department of Veterinary Medicine, College 
      of Bioresource Sciences, Nihon University, Kameino, Fujisawa, Kanagawa, Japan.
FAU - Okabayashi, Ken
AU  - Okabayashi K
AD  - Laboratory of Veterinary Biochemistry, Department of Veterinary Medicine, College 
      of Bioresource Sciences, Nihon University, Kameino, Fujisawa, Kanagawa, Japan.
FAU - Sugiya, Hiroshi
AU  - Sugiya H
AD  - Laboratory of Veterinary Biochemistry, Department of Veterinary Medicine, College 
      of Bioresource Sciences, Nihon University, Kameino, Fujisawa, Kanagawa, Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20151102
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Microtubule-Associated Proteins)
RN  - 103107-01-3 (Fibroblast Growth Factor 2)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.10.1 (Receptor, Fibroblast Growth Factor, Type 2)
RN  - EC 2.7.11.1 (Oncogene Protein v-akt)
SB  - IM
MH  - Animals
MH  - Cell Differentiation/drug effects
MH  - Cells, Cultured
MH  - Dogs
MH  - Fibroblast Growth Factor 2/*pharmacology
MH  - Gene Expression Regulation/drug effects
MH  - Male
MH  - Mesenchymal Stem Cells/cytology/*drug effects
MH  - Microtubule-Associated Proteins/genetics
MH  - Neurons/*cytology/drug effects
MH  - Oncogene Protein v-akt/genetics/metabolism
MH  - Phosphatidylinositol 3-Kinases/genetics/metabolism
MH  - Phosphorylation/drug effects
MH  - Receptor, Fibroblast Growth Factor, Type 2/genetics/*metabolism
MH  - Signal Transduction/*drug effects
PMC - PMC4629880
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2015/11/03 06:00
MHDA- 2016/06/21 06:00
PMCR- 2015/11/02
CRDT- 2015/11/03 06:00
PHST- 2015/04/27 00:00 [received]
PHST- 2015/10/09 00:00 [accepted]
PHST- 2015/11/03 06:00 [entrez]
PHST- 2015/11/03 06:00 [pubmed]
PHST- 2016/06/21 06:00 [medline]
PHST- 2015/11/02 00:00 [pmc-release]
AID - PONE-D-15-15548 [pii]
AID - 10.1371/journal.pone.0141581 [doi]
PST - epublish
SO  - PLoS One. 2015 Nov 2;10(11):e0141581. doi: 10.1371/journal.pone.0141581. 
      eCollection 2015.