Growth arrest-specific gene 6 protein promotes the proliferation and migration of endothelial progenitor cells through the PI3K/AKT signaling pathway.
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.
Department of Geriatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.
Pei-Yuan
PY
Zuo
Department of Geriatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.
Xing-Lin
XL
Chen
Department of Geriatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.
Ying-Hong
YH
Lei
Department of Geriatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.
Cheng-Yun
CY
Liu
Department of Geriatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.
Yu-Wei
YW
Liu
D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D066026:Endothelial Progenitor Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism; D005312:Fetal Blood / Q000166:cytology / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism / Q000494:pharmacology*; D018919:Neovascularization, Physiologic; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics* / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D000099255:Growth Arrest-Specific Protein 6
D048049:Extracellular Signal-Regulated MAP Kinases; D036341:Intercellular Signaling Peptides and Proteins; D019869:Phosphatidylinositol 3-Kinases; D047428:Protein Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D000099255:Growth Arrest-Specific Protein 6