The aim of the present study was to investigate the effect of metformin on endothelial progenitor cell (EPC) migration and to explore the possible mechanisms. EPCs were treated with metformin, and the migration of EPCs was evaluated by wound healing and Matrigel invasion assays. We also examined the expression levels of of MMP-2 and MMP-9 in EPCs with or without metformin treatment via RT-PCR and western blot analysis, and activities of MMP-2 and MMP-9 in EPCs under different conditions was examined by zymography. Moreover, we also assessed the AMPK/mTOR/autophagy pathway to explore the possible mechanisms. Metformin treatment significantly downregulated matrix metalloproteinase-2 (MMP-2) and MMP-9 expression, and subsequently decreased the migration of EPCs. Increased levels of phosphorylated (p)-AMPK and LC3II expression, as well as decreased levels of p-mTOR and p62 contributed to this phenomenon. The AMPK inhibitor compound C reversed the effect exerted by metformin. In conclusion, our results showed that metformin inhibited the migration of EPCs by decreasing MMP-2 and MMP-9. The AMPK/mTOR/autophagy pathway was demonstrated to be involved in the regulatory mechanisms.
基金：
This study was supported by grants from the Scientific and Technological Research Projects of Jiangsu Province (no. BL2014043), Graduate Research and Innovation Program in Colleges and Universities of Jiangsu Province (no. KYLX15_1202).
第一作者机构：[1]Department of Vascular Surgery, The Second Affiliated Hospital of Soochow University,Suzhou, Jiangsu 215000, P.R. China
共同第一作者：
通讯作者：
通讯机构：[*1]Department of Vascular Surgery, The Second Affiliated Hospital of Soochow University, 1055 Sanxiang Road, Suzhou, Jiangsu 215000, P.R. China
推荐引用方式(GB/T 7714)：
WEN-DONG LI,NENG-PING LI,DAN-DAN SONG,et al.Metformin inhibits endothelial progenitor cell migration by decreasing matrix metalloproteinases, MMP-2 and MMP-9, via the AMPK/mTOR/autophagy pathway[J].INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE.2017,39(5):1262-1268.doi:10.3892/ijmm.2017.2929.
APA：
WEN-DONG LI,NENG-PING LI,DAN-DAN SONG,JIAN-JIE RONG,AI-MIN QIAN&XIAO-QIANG LI.(2017).Metformin inhibits endothelial progenitor cell migration by decreasing matrix metalloproteinases, MMP-2 and MMP-9, via the AMPK/mTOR/autophagy pathway.INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE,39,(5)
MLA：
WEN-DONG LI,et al."Metformin inhibits endothelial progenitor cell migration by decreasing matrix metalloproteinases, MMP-2 and MMP-9, via the AMPK/mTOR/autophagy pathway".INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE 39..5(2017):1262-1268
