Blocking of autocrine IGF-1 reduces viability of human umbilical cord mesenchymal stem cells via inhibition of the Akt/Gsk-3β signaling pathway.
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.
['Wang|Qi|Q|', 'Zhang|Fenxi|F|', 'Hong|Yan|Y|']
D000906:Antibodies D017209:Apoptosis D002470:Cell Survival D002478:Cells, Cultured D019938:Cyclin D1 D050759:Cyclin-Dependent Kinase Inhibitor p21 D059565:G2 Phase Cell Cycle Checkpoints D000071679:Glycogen Synthase Kinase 3 beta D006801:Humans D007334:Insulin-Like Growth Factor I D059630:Mesenchymal Stem Cells D019950:Mitogen-Activated Protein Kinase 1 D048052:Mitogen-Activated Protein Kinase 3 D051057:Proto-Oncogene Proteins c-akt D017526:Receptor, IGF Type 1 D015398:Signal Transduction D014470:Umbilical Cord
autocrine cell   viability human  umbilical  cord  mesenchymal  stem  cells cell apoptosis insulin-like growth factor-1 Akt  signaling