PMID- 26713735
OWN - NLM
STAT- MEDLINE
DCOM- 20160701
LR  - 20211203
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 10
IP  - 12
DP  - 2015
TI  - Cell Signaling and Differential Protein Expression in Neuronal Differentiation of 
      Bone Marrow Mesenchymal Stem Cells with Hypermethylated Salvador/Warts/Hippo 
      (SWH) Pathway Genes.
PG  - e0145542
LID - 10.1371/journal.pone.0145542 [doi]
LID - e0145542
AB  - Human mesenchymal stem cells (MSCs) modified by targeting DNA hypermethylation of 
      genes in the Salvador/Warts/Hippo pathway were induced to differentiate into 
      neuronal cells in vitro. The differentiated cells secreted a significant level of 
      brain-derived neurotrophy factor (BDNF) and the expression of BDNF receptor 
      tyrosine receptor kinase B (TrkB) correlated well with the secretion of BDNF. In 
      the differentiating cells, CREB was active after the binding of growth factors to 
      induce phosphorylation of ERK in the MAPK/ERK pathway. Downstream of 
      phosphorylated CREB led to the functional maturation of differentiated cells and 
      secretion of BDNF, which contributed to the sustained expression of pERK and 
      pCREB. In summary, both PI3K/Akt and MAPK/ERK signaling pathways play important 
      roles in the neuronal differentiation of MSCs. The main function of the PI3K/Akt 
      pathway is to maintain cell survival during neural differentiation; whereas the 
      role of the MAPK/ERK pathway is probably to promote the maturation of 
      differentiated MSCs. Further, cellular levels of protein kinase C epsilon type 
      (PKC-epsilon) and kinesin heavy chain (KIF5B) increased with time of induction, whereas 
      the level of NME/NM23 nucleoside diphosphate kinase 1 (Nm23-H1) decreased during 
      the time course of differentiation. The correlation between PKC-epsilon and TrkB 
      suggested that there is cross-talk between PKC-epsilon and the PI3K/Akt signaling 
      pathway.
FAU - Tzeng, Hui-Hung
AU  - Tzeng HH
AD  - Department of Chemical Engineering, Systems Biology and Tissue Engineering 
      Research Center, National Chung Cheng University, Minhsiung, Chiayi, 621 Taiwan.
FAU - Hsu, Chi-Hung
AU  - Hsu CH
AD  - Department of Chemical Engineering, Systems Biology and Tissue Engineering 
      Research Center, National Chung Cheng University, Minhsiung, Chiayi, 621 Taiwan.
FAU - Chung, Ting-Hao
AU  - Chung TH
AD  - Department of Chemical Engineering, Systems Biology and Tissue Engineering 
      Research Center, National Chung Cheng University, Minhsiung, Chiayi, 621 Taiwan.
FAU - Lee, Wen-Chien
AU  - Lee WC
AD  - Department of Chemical Engineering, Systems Biology and Tissue Engineering 
      Research Center, National Chung Cheng University, Minhsiung, Chiayi, 621 Taiwan.
FAU - Lin, Chi-Hsien
AU  - Lin CH
AD  - Department of Chemical Engineering, Systems Biology and Tissue Engineering 
      Research Center, National Chung Cheng University, Minhsiung, Chiayi, 621 Taiwan.
FAU - Wang, Wan-Chen
AU  - Wang WC
AD  - Department of Chemical Engineering, Systems Biology and Tissue Engineering 
      Research Center, National Chung Cheng University, Minhsiung, Chiayi, 621 Taiwan.
FAU - Hsiao, Chen-Yu
AU  - Hsiao CY
AD  - Department of Chemical Engineering, Systems Biology and Tissue Engineering 
      Research Center, National Chung Cheng University, Minhsiung, Chiayi, 621 Taiwan.
FAU - Leu, Yu-Wei
AU  - Leu YW
AD  - Department of Life Science, National Chung Cheng University, Minhsiung, Chiayi, 
      621, Taiwan.
FAU - Wang, Tzu-Hsien
AU  - Wang TH
AD  - Department of Chemical Engineering, Systems Biology and Tissue Engineering 
      Research Center, National Chung Cheng University, Minhsiung, Chiayi, 621 Taiwan.
LA  - eng
PT  - Journal Article
DEP - 20151229
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Cell Cycle Proteins)
RN  - EC 2.7.1.- (LATS1 protein, human)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
SB  - IM
MH  - Brain-Derived Neurotrophic Factor/metabolism
MH  - Cell Cycle Proteins/metabolism
MH  - *Cell Differentiation
MH  - Cell Survival
MH  - *DNA Methylation
MH  - *Gene Expression Regulation
MH  - Hippo Signaling Pathway
MH  - Humans
MH  - Mesenchymal Stem Cells/*cytology
MH  - Neurons/*cytology/metabolism
MH  - Protein Serine-Threonine Kinases/metabolism
MH  - *Signal Transduction
PMC - PMC4699852
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2015/12/30 06:00
MHDA- 2016/07/02 06:00
PMCR- 2015/12/29
CRDT- 2015/12/30 06:00
PHST- 2015/08/25 00:00 [received]
PHST- 2015/12/04 00:00 [accepted]
PHST- 2015/12/30 06:00 [entrez]
PHST- 2015/12/30 06:00 [pubmed]
PHST- 2016/07/02 06:00 [medline]
PHST- 2015/12/29 00:00 [pmc-release]
AID - PONE-D-15-37379 [pii]
AID - 10.1371/journal.pone.0145542 [doi]
PST - epublish
SO  - PLoS One. 2015 Dec 29;10(12):e0145542. doi: 10.1371/journal.pone.0145542. 
      eCollection 2015.