title: Metformin regulates differentiation of bone marrow-derived endothelial progenitor cells via multiple mechanisms.
abstract: 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-p70S6K 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-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.
  
  
  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.
authors: Department of Vascular Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, China.
authors: Wen-Dong
authors: WD
authors: Li
authors: Department of Vascular Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, China.
authors: Xiao-Long
authors: XL
authors: Du
authors: Department of Vascular Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, China.
authors: Ai-Min
authors: AM
authors: Qian
authors: Department of Vascular Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, China.
authors: Nan
authors: N
authors: Hu
authors: Department of Vascular Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, China.
authors: Ling-Shang
authors: LS
authors: Kong
authors: Department of Vascular Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, China.
authors: Sen
authors: S
authors: Wei
authors: Department of Vascular Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, China.
authors: Cheng-Long
authors: CL
authors: Li
authors: Department of Vascular Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, China. Electronic address: flytsg@126.com.
authors: Xiao-Qiang
authors: XQ
authors: Li
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000818:Animals; D001343:Autophagy / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects*; D066026:Endothelial Progenitor Cells / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000494:pharmacology; D008687:Metformin / Q000494:pharmacology*; D008954:Models, Biological; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014841:von Willebrand Factor / Q000378:metabolism
chemical_list: D007004:Hypoglycemic Agents; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D014841:von Willebrand Factor; D009569:Nitric Oxide; D008687:Metformin; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D055372:AMP-Activated Protein Kinases
keywords: Adenosine monophosphate activated protein kinase; Autophagy; Differentiation; Endothelial nitric oxide synthase; Endothelial progenitor cells; Metformin