Erythropoietin promotes endothelial progenitor cells proliferation depending on PI3k/Akt pathway

doi:10.3969/j.issn.2095-4344.2014.45.018

Abstract

Abstract:

BACKGROUND: It has been proved that erythropoietin can promotes angiogenesis in injured tissue, which is closely related to the proliferation and differentiation of endothelial progenitor cells. However, the involved mechanism remains unclear yet.

OBJECTIVE: To investigate the effect of erythropoietin on the function and activity of bone marrow-derived endothelial progenitor cells in mice, and to explore the signal pathway.

METHODS: The endothelial progenitor cells from the bone marrow of mice were separated by means of density gradient centrifugation and then cultured. The cells were preconditioned by specific inhibitor of PI3K (LY294002), and were divided into the following groups: EGM-2 group, three erythropoietin preconditioned groups (the concentrations of erythropoietin in medium were 1, 5, 10 U/mL respectively), erythropoietin+LY group (10 U/mL erythropoietin and 10 mmol/L LY294002 in medium), LY group (10 mmol/L LY294002 in medium), dimethyl sulfoxide group (1 mL/L dimethyl sulfoxide in medium). The cell proliferation and apoptosis were evaluated by cell counting kit-8 and flow cytometry respectively. The contents of endothelial nitric oxide synthase and vascular endothelial growth factor in cell lysates were detected by the method of ELISA, and the expressions of Akt and p-Akt were by western blot assay.

RESULTS AND CONCLUSION: Erythropoietin could promote the proliferation of endothelial progenitor cells in a dose-dependent manner, which was, however, completely inhibited by LY294002. The apoptosis rate in the erythropoietin preconditioned groups was significantly lower than that in the erythropoietin+LY group. The contents of endothelial nitric oxide synthase and vascular endothelial growth factor in cell lysates of LY group and erythropoietin+LY group were significantly lower than those in the erythropoietin groups. There was no difference in Akt expression found in each group, while the p-Akt expression in the erythropoietin+LY group was significantly lower than that in the erythropoietin groups. The above results reveal that erythropoietin can promote the proliferation of endothelial progenitor cells and decrease the cell apoptosis, which is depending on PI3K/Akt signal pathway.

中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程

全文链接：

Key words: endothelial cells, erythropoietin, phosphatidylinositol 3-kinase

CLC Number:

R394.2

Wu Hai-wei, Zhang Lei, Hu Ruo-yu, Li Hao, Jing Hua, Dong Guo-hua, Xu Biao, Li De-min . Erythropoietin promotes endothelial progenitor cells proliferation depending on PI3k/Akt pathway[J]. Chinese Journal of Tissue Engineering Research, 2014, 18(45): 7312-7319.

Figures/Tables 13

References

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