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Metformin inhibits endothelial progenitor cell migration by decreasing matrix metalloproteinases, MMP-2 and MMP-9, via the AMPK/mTOR/autophagy pathway.
Int J Mol Med. 2017 May; 39(5):1262-1268.IJ

Abstract

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.

Authors+Show Affiliations

Department of Vascular Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215000, P.R. China.Department of Vascular Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215000, P.R. China.Department of Vascular Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215000, P.R. China.Department of Vascular Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215000, P.R. China.Department of Vascular Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215000, P.R. China.Department of Vascular Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215000, P.R. China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28339020

Citation

Li, Wen-Dong, 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, vol. 39, no. 5, 2017, pp. 1262-1268.
Li WD, Li NP, Song DD, et al. Metformin inhibits endothelial progenitor cell migration by decreasing matrix metalloproteinases, MMP-2 and MMP-9, via the AMPK/mTOR/autophagy pathway. Int J Mol Med. 2017;39(5):1262-1268.
Li, W. D., Li, N. P., Song, D. D., Rong, J. J., Qian, A. M., & Li, X. Q. (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), 1262-1268. https://doi.org/10.3892/ijmm.2017.2929
Li WD, et al. Metformin Inhibits Endothelial Progenitor Cell Migration By Decreasing Matrix Metalloproteinases, MMP-2 and MMP-9, Via the AMPK/mTOR/autophagy Pathway. Int J Mol Med. 2017;39(5):1262-1268. PubMed PMID: 28339020.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Metformin inhibits endothelial progenitor cell migration by decreasing matrix metalloproteinases, MMP-2 and MMP-9, via the AMPK/mTOR/autophagy pathway. AU - Li,Wen-Dong, AU - Li,Neng-Ping, AU - Song,Dan-Dan, AU - Rong,Jian-Jie, AU - Qian,Ai-Min, AU - Li,Xiao-Qiang, Y1 - 2017/03/21/ PY - 2016/10/25/received PY - 2017/03/15/accepted PY - 2017/3/25/pubmed PY - 2017/7/1/medline PY - 2017/3/25/entrez SP - 1262 EP - 1268 JF - International journal of molecular medicine JO - Int. J. Mol. Med. VL - 39 IS - 5 N2 - 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. SN - 1791-244X UR - https://www.unboundmedicine.com/medline/citation/28339020/Metformin_inhibits_endothelial_progenitor_cell_migration_by_decreasing_matrix_metalloproteinases_MMP_2_and_MMP_9_via_the_AMPK/mTOR/autophagy_pathway_ L2 - http://www.spandidos-publications.com/ijmm/39/5/1262 DB - PRIME DP - Unbound Medicine ER -