Growth arrest-specific gene 6 protein promotes the proliferation and migration of endothelial progenitor cells through the PI3K/AKT signaling pathway

Zuo,Pei-Yuan; Chen,Xing-Lin; Lei,Ying-Hong; Liu,Cheng-Yun; Liu,Yu-Wei

doi:10.3892/ijmm.2014.1754

Growth arrest-specific gene 6 protein promotes the proliferation and migration of endothelial progenitor cells through the PI3K/AKT signaling pathway

Authors:
- Pei-Yuan Zuo
- Xing-Lin Chen
- Ying-Hong Lei
- Cheng-Yun Liu
- Yu-Wei Liu
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Affiliations: Department of Geriatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China
Published online on: April 24, 2014 https://doi.org/10.3892/ijmm.2014.1754
Pages: 299-306

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Abstract

Endothelial progenitor cells (EPCs) play an important role in endothelial repair and vascular regeneration. Growth arrest-speciﬁc gene 6 (Gas6) is a novel key regulator of the vascular system, which is linked to a number of cardiovascular diseases. However, the effects of Gas6 on EPCs have not been elucidated to date. The present study was designed to determine the biological function of EPCs treated with Gas6 and to eludicate the underlying mechanisms. EPCs were isolated from umbilical cord blood and treated with various concentrations (25, 50, 100 and 200 ng/ml) of Gas6. The proliferation, migration and angiogenesis of the Gas6-treated EPCs were evaluated by MTT assay, Transwell assay and in vitro tube formation assay, respectively. The phosphorylation status of AKT and ERK was evaluated by western blot analysis. The results demonstrated that treatment with Gas6 enhanced the proliferation and migration of the EPCs in a dose-dependent manner. However, Gas6 did not promote the differentiation of EPCs on Matrigel. Gas6 induced the phosphorylation of AKT, but not that of ERK. The enhanced proliferation and migration induced by Gas6 was markedly suppressed by the inhibitor of PI3K but not by that of ERK. These results suggest that Gas6 activates the AKT signaling pathway, which, in turn, promotes the proliferation and migration of EPCs.

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