Metformin regulates differentiation of bone marrow-derived endothelial progenitor cells via multiple mechanisms

被引:18
作者
Li, Wen-Dong [1 ]
Du, Xiao-Long [1 ]
Qian, Ai-Min [1 ]
Hu, Nan [1 ]
Kong, Ling-Shang [1 ]
Wei, Sen [1 ]
Li, Cheng-Long [1 ]
Li, Xiao-Qiang [1 ]
机构
[1] Soochow Univ, Affiliated Hosp 2, Dept Vasc Surg, Suzhou 215000, Jiangsu, Peoples R China
基金
中国国家自然科学基金;
关键词
Metformin; Endothelial progenitor cells; Differentiation; Autophagy; Endothelial nitric oxide synthase; Adenosine monophosphate activated protein kinase; ACTIVATED PROTEIN-KINASE; OSTEOBLASTIC MC3T3-E1 CELLS; DEEP-VEIN THROMBOSIS; MESENCHYMAL TRANSITION; VASCULAR COMPLICATIONS; UP-REGULATION; AUTOPHAGY; ENOS; PROLIFERATION; CONTRIBUTES;
D O I
10.1016/j.bbrc.2015.08.091
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Objective: The aim of this study was to investigate the effect of metformin on endothelial progenitor cells (EPCs) differentiation and the possible mechanisms. Methods: EPCs were treated with metformin and differentiation, migration and tube formation of EPCs were evaluated. Moreover, we also assessed the AMPK-mTOR-p70SEK pathway, AMPK related autophagy pathway and eNOS-NO pathway to explore the mechanisms. Results: Metformin treatment could significantly increase differentiation of EPCs. On the mechanisms, increased level of AMPKand eNOS phosphorylation, LC3 expression and NO production, and decreased mTOR, p70 S6K as well as TGF-beta expression were found in EPCs. The AMPK inhibitor compound C, Atg5 knocking-down and eNOS inhibitor L-NAME could reverse the effect exerted by metformin. Conclusions: Our results here showed that metformin could regulate the differentiation of EPCs. Autophagy related pathway and AMPK-eNOS-NO pathway were involved in the mechanisms. (C) 2015 Elsevier Inc. All rights reserved.
引用
收藏
页码:803 / 809
页数:7
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