Blocking of autocrine IGF-1 reduces viability of human umbilical cord mesenchymal stem cells via inhibition of the Akt/Gsk-3β signaling pathway

Wang,Qi; Zhang,Fenxi; Hong,Yan

doi:10.3892/mmr.2018.8445

Blocking of autocrine IGF-1 reduces viability of human umbilical cord mesenchymal stem cells via inhibition of the Akt/Gsk-3β signaling pathway

Authors:
- Qi Wang
- Fenxi Zhang
- Yan Hong
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Affiliations: Department of Histology and Embryology, Guizhou Medical University, Guiyang, Guizhou 550004, P.R. China
Published online on: January 17, 2018 https://doi.org/10.3892/mmr.2018.8445
Pages: 4681-4687

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Abstract

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 µg/ml αIR‑3, a specific IGF‑1R antibody, for 24 h. The cells cultured in medium without αIR‑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 αIR‑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 αIR‑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 3β (GSK‑3β), p‑p70 S6 kinase and cyclin D1 were markedly reduced and p21 expression was markedly increased in the αIR‑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 αIR‑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‑3β signaling pathway.

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