PMID- 29344668
OWN - NLM
STAT- MEDLINE
DCOM- 20180814
LR  - 20211022
IS  - 1791-3004 (Electronic)
IS  - 1791-2997 (Linking)
VI  - 17
IP  - 3
DP  - 2018 Mar
TI  - Blocking of autocrine IGF-1 reduces viability of human umbilical cord mesenchymal 
      stem cells via inhibition of the Akt/Gsk-3beta signaling pathway.
PG  - 4681-4687
LID - 10.3892/mmr.2018.8445 [doi]
AB  - Human umbilical cord mesenchymal stem cells (hUCMSCs) are able to secrete growth 
      factors, such as hepatocyte growth factor, vascular endothelial growth factor and 
      insulin‑like growth factor‑1 (IGF‑1). The secretion of these growth factors by 
      transplanted hUCMSCs have been identified to stimulate the growth of the host 
      cells in the target organs or tissues. The aim of the present study was to 
      investigate the effect of autocrine IGF‑1 on cell viability of hUCMSCs. The 
      expression levels of IGF‑1 and the IGF‑1 receptor (IGF‑1R) in hUCMSCs were 
      identified using immunocytochemistry staining. In order to block autocrine IGF‑1, 
      hUCMSCs were treated with 5 microg/ml alphaIR‑3, a specific IGF‑1R antibody, for 24 h. 
      The cells cultured in medium without alphaIR‑3 were used as the control group. Cell 
      viability, apoptosis, cell cycle and the proliferation‑associated proteins were 
      quantified using an MTT assay, flow cytometry and western blotting. The findings 
      of the present study revealed that IGF‑1 and IGF‑1R were positively expressed in 
      hUCMSCs. Treatment with alphaIR‑3 significantly reduced cell viability and increased 
      apoptosis of hUCMSCs (P<0.01). Cell cycle analysis indicated that the number of 
      cells in the G2/M phase was reduced in the alphaIR‑3‑treated group compared with the 
      control group. Western blotting revealed that the expression levels of 
      phosphorylated (p)‑protein kinase B (Akt), p‑glycogen synthase kinase 3beta 
      (GSK‑3beta), p‑p70 S6 kinase and cyclin D1 were markedly reduced and p21 expression 
      was markedly increased in the alphaIR‑3‑treated group as compared with the control 
      group (P<0.05). However, no significant difference was identified in the 
      p‑extracellular‑signal regulated kinase 1/2 expression when the alphaIR‑3 treatment 
      group was compared with the control group. (P>0.05). The findings of the present 
      study suggested that the autocrine IGF‑1 from hUCMSCs may be capable of 
      influencing cell viability of hUCMSCs, which may be associated with activation of 
      Akt/GSK‑3beta signaling pathway.
FAU - Wang, Qi
AU  - Wang Q
AD  - Department of Histology and Embryology, Guizhou Medical University, Guiyang, 
      Guizhou 550004, P.R. China.
FAU - Zhang, Fenxi
AU  - Zhang F
AD  - Department of Histology and Embryology, Guizhou Medical University, Guiyang, 
      Guizhou 550004, P.R. China.
FAU - Hong, Yan
AU  - Hong Y
AD  - Department of Histology and Embryology, Guizhou Medical University, Guiyang, 
      Guizhou 550004, P.R. China.
LA  - eng
PT  - Journal Article
DEP - 20180117
PL  - Greece
TA  - Mol Med Rep
JT  - Molecular medicine reports
JID - 101475259
RN  - 0 (Antibodies)
RN  - 0 (Cyclin-Dependent Kinase Inhibitor p21)
RN  - 136601-57-5 (Cyclin D1)
RN  - 67763-96-6 (Insulin-Like Growth Factor I)
RN  - EC 2.7.10.1 (Receptor, IGF Type 1)
RN  - EC 2.7.11.1 (Glycogen Synthase Kinase 3 beta)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3)
SB  - IM
MH  - Antibodies/immunology/pharmacology
MH  - Apoptosis/drug effects
MH  - Cell Survival/drug effects
MH  - Cells, Cultured
MH  - Cyclin D1/metabolism
MH  - Cyclin-Dependent Kinase Inhibitor p21/metabolism
MH  - G2 Phase Cell Cycle Checkpoints/drug effects
MH  - Glycogen Synthase Kinase 3 beta/*metabolism
MH  - Humans
MH  - Insulin-Like Growth Factor I/immunology/*metabolism
MH  - Mesenchymal Stem Cells/cytology/metabolism
MH  - Mitogen-Activated Protein Kinase 1/metabolism
MH  - Mitogen-Activated Protein Kinase 3/metabolism
MH  - Proto-Oncogene Proteins c-akt/*metabolism
MH  - Receptor, IGF Type 1/metabolism
MH  - Signal Transduction/drug effects
MH  - Umbilical Cord/cytology
OTO - NOTNLM
OT  - cell viability
OT  - human umbilical cord mesenchymal stem cells
OT  - cell apoptosis
OT  - insulin-like growth factor-1
OT  - autocrine
OT  - Akt signaling
EDAT- 2018/01/19 06:00
MHDA- 2018/08/15 06:00
CRDT- 2018/01/19 06:00
PHST- 2016/03/24 00:00 [received]
PHST- 2017/05/09 00:00 [accepted]
PHST- 2018/01/19 06:00 [pubmed]
PHST- 2018/08/15 06:00 [medline]
PHST- 2018/01/19 06:00 [entrez]
AID - 10.3892/mmr.2018.8445 [doi]
PST - ppublish
SO  - Mol Med Rep. 2018 Mar;17(3):4681-4687. doi: 10.3892/mmr.2018.8445. Epub 2018 Jan 
      17.