PMID- 29141367
OWN - NLM
STAT- MEDLINE
DCOM- 20180629
LR  - 20181202
IS  - 0376-2491 (Print)
IS  - 0376-2491 (Linking)
VI  - 97
IP  - 41
DP  - 2017 Nov 7
TI  - [Differentiation of induced pluripotent stem cells into neural stem cells induced 
      by brain-derived neurotrophic factor via Wnt/beta-catenin and extracellular 
      signal-regulated kinase/mitogen-activated protein kinases signal pathway].
PG  - 3263-3268
LID - 10.3760/cma.j.issn.0376-2491.2017.41.014 [doi]
AB  - Objective: To investigate the mechanism of brain-derived neurotrophic factor 
      (BDNF) promoting induced pluripotent stem cells (iPSCs) to differentiate into 
      neural stem cells (NSCs) via Wnt/beta-catenin and extracellular signal-regulated 
      kinase/mitogen-activated protein kinases (ERK/MAPK) signal pathways. Methods: 
      iPSCs were cultured and identified. The iPSCs were induced to differentiate into 
      NSCs by BDNF and retinoic acid (RA). Nestin was detected by immunofluorescence 
      and flow cytometry after iPSCs differentiated. The technique of small interfering 
      RNA (siRNA) was used to silence the gene expression of beta-catenin and ERK, and 
      iPSCs were divided into control group, BDNF group (adding 10 mug/L BDNF), 
      siRNA-ERK/BDNF group (transfected with siRNA-ERK and adding 10 mug/L BDNF) and 
      siRNA-beta-catenin/BDNF group (transfected with siRNA-beta-catenin and adding 10 mug/L 
      BDNF). Real-time polymerase chain reaction (RT-PCR) and Western blotting were 
      used to detect the mRNA and protein expression of key elements of Wnt/beta-catenin 
      and ERK/MAPK signaling pathways, included beta-catenin, ERK1/2, c-fos, c-jun, and 
      c-myc. The least significant difference test was used when data were compared 
      between groups. Results: The immunofluorescence showed that iPSCs expressed 
      octamer-binding transcription factor-4 (Oct4), SRY-related HMG box protein-2 
      (Sox2) and Nanog genes. The flow cytometry showed that Nestin-positive cells were 
      78.7% for BDNF and 43.5% for RA, and it was only 7.8% for routine medium. 
      Compared with those in the control group, the mRNA expression of beta-catenin, 
      ERK1/2, c-fos, c-jun, and c-myc in the BDNF group were upregulated significantly 
      (t=2.80, 2.318, 2.255, 1.799, 1.582, 1.663, all P<0.05), and the same results 
      were acquired with the protein expression (t=2.805, 2.318, 2.255, 1.799, 1.582, 
      1.663, all P<0.050). Compared with those in BDNF group, the mRNA and protein 
      expression of ERK1/2 in siRNA-ERK/BDNF group down-regulated obviously (t=1.917, 
      2.042, 1.673, 1.540, all P<0.05), and the mRNA and protein expression of c-fos 
      and c-jun were down-regulated (t=1.022, 0.907, 0.848, 0.801, all P<0.05). 
      However, the mRNA and protein expression of beta-catenin and c-myc were not 
      suppressed by siRNA-ERK (t=0.216, 0.185, 0.097, 0.112, all P>0.05). In 
      siRNA-beta-catenin/BDNF group, the mRNA and protein expression of beta-catenin and 
      c-myc was obviously down-regulated when compared with those in BDNF group 
      (t=3.104, 2.774, 2.235, 1.911, all P<0.05), and expression of ERK1/2, c-fos and 
      c-jun were down-regulated too (t=0.776-1.192, all P<0.05). Conclusion: BDNF 
      promotes the differentiation of iPSCs by activating Wnt/beta-catenin and ERK/MAPK 
      signal pathway, there should be cross-talk between the two signal pathways, and 
      c-fos and c-jun may be common nuclear transcription factors.
FAU - Chen, S Q
AU  - Chen SQ
AD  - Neuroimaging Research Center, the Affiliated Suzhou Hospital of Nanjing Medical 
      University, Suzhou 215001, China.
FAU - Huang, M
AU  - Huang M
FAU - Liu, C L
AU  - Liu CL
FAU - Shen, Y Y
AU  - Shen YY
FAU - Cai, Q
AU  - Cai Q
FAU - Wang, P J
AU  - Wang PJ
LA  - chi
PT  - Journal Article
PL  - China
TA  - Zhonghua Yi Xue Za Zhi
JT  - Zhonghua yi xue za zhi
JID - 7511141
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (beta Catenin)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
SB  - IM
MH  - Brain-Derived Neurotrophic Factor/*physiology
MH  - *Cell Differentiation
MH  - Extracellular Signal-Regulated MAP Kinases/metabolism
MH  - Humans
MH  - *Induced Pluripotent Stem Cells
MH  - *Neural Stem Cells
MH  - RNA, Small Interfering
MH  - Signal Transduction
MH  - Wnt Signaling Pathway
MH  - beta Catenin/*physiology
OTO - NOTNLM
OT  - Brain-derived neurotrophic factor
OT  - Extracellular signal-regulated kinase/mitogen-activated protein kinases signal 
      pathway
OT  - Induced pluripotent stem cells
OT  - Neural stem cells
OT  - Wnt/beta-catenin signal pathway
EDAT- 2017/11/17 06:00
MHDA- 2018/06/30 06:00
CRDT- 2017/11/17 06:00
PHST- 2017/11/17 06:00 [entrez]
PHST- 2017/11/17 06:00 [pubmed]
PHST- 2018/06/30 06:00 [medline]
AID - 10.3760/cma.j.issn.0376-2491.2017.41.014 [doi]
PST - ppublish
SO  - Zhonghua Yi Xue Za Zhi. 2017 Nov 7;97(41):3263-3268. doi: 
      10.3760/cma.j.issn.0376-2491.2017.41.014.