Metformin inhibits endothelial progenitor cell migration by decreasing matrix metalloproteinases, MMP-2 and MMP-9, via the AMPK/mTOR/autophagy pathway.
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.
Department of Vascular Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215000, P.R. China.
Wen-Dong
WD
Li
Department of Vascular Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215000, P.R. China.
Neng-Ping
NP
Li
Department of Vascular Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215000, P.R. China.
Dan-Dan
DD
Song
Department of Vascular Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215000, P.R. China.
Jian-Jie
JJ
Rong
Department of Vascular Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215000, P.R. China.
Ai-Min
AM
Qian
Department of Vascular Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215000, P.R. China.
Xiao-Qiang
XQ
Li
D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D001343:Autophagy / Q000187:drug effects*; D002465:Cell Movement / Q000187:drug effects; D066026:Endothelial Progenitor Cells / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D008687:Metformin / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
D008687:Metformin; D058570:TOR Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9