Li Wen-Dong, Du Xiao-Long, Qian Ai-Min, Hu Nan, Kong Ling-Shang, Wei Sen, Li Cheng-Long, Li Xiao-Qiang
Department of Vascular Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, China.
Department of Vascular Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, China.
Biochem Biophys Res Commun. 2015 Oct 2;465(4):803-9. doi: 10.1016/j.bbrc.2015.08.091. Epub 2015 Aug 28.
The aim of this study was to investigate the effect of metformin on endothelial progenitor cells (EPCs) differentiation and the possible mechanisms.
EPCs were treated with metformin and differentiation, migration and tube formation of EPCs were evaluated. Moreover, we also assessed the AMPK-mTOR-p70S6K pathway, AMPK related autophagy pathway and eNOS-NO pathway to explore the mechanisms.
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-β 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.
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.
本研究旨在探讨二甲双胍对内皮祖细胞（EPCs）分化的影响及其可能机制。
用二甲双胍处理EPCs，并评估EPCs的分化、迁移和管腔形成。此外，我们还评估了AMPK-mTOR-p70S6K途径、AMPK相关自噬途径和eNOS-NO途径以探索其机制。
二甲双胍处理可显著增加EPCs的分化。在机制方面，发现EPCs中AMPK和eNOS磷酸化水平升高、LC3表达和NO生成增加，而mTOR、p70 S6K以及TGF-β表达降低。AMPK抑制剂化合物C、Atg5基因敲低和eNOS抑制剂L-NAME可逆转二甲双胍所发挥的作用。
我们的研究结果表明，二甲双胍可调节EPCs的分化。自噬相关途径和AMPK-eNOS-NO途径参与了其机制。
