title: Effects of hepatocyte growth factor-mediated activation of Dll4-Notch-Hey2 signaling pathway.
abstract: BACKGROUND
  Hepatocyte growth factor (HGF) treats ischemic disease by promoting arteriogenesis, however, its mechanism of action is not known. The notch signaling pathway plays an important role in neovascularization. The relationship between the proliferation and migration ability of artery endothelial cells and the Dll4-Notch-Hey2 signaling pathway in the process of arteriogenesis was investigated as a mechanism of action of HGF.
  
  
  METHODS
  Based on the prophase study cells and supernatant were harvested at the indicated time after human femoral artery endothelial cells (HFAECs) were infected with adenovirus-HGF (Ad-HGF) at 200 pfu/cell. Cells were analyzed for HGF expression and Notch1, Dll4 and Hey2 expression by ELISA and reverse transcription-PCR (RT-PCR). The changes in the proliferation and migration ability of HFAECs were observed by MTT and Transwell migration experiments. Ad-GFP-infected HFAECs were used as control.
  
  
  RESULTS
  Compared with the control group the Ad-HGF group's HGF expression was not increased with time, and the induction by HGF of Notch1, Dll4 and Hey2 gene transcription was not enhanced with an increase of HGF. The proliferation ability of Ad-HGF-transduced HFAECs was enhanced and their migration ability was also enhanced in the presence of HGF.
  
  
  CONCLUSIONS
  Through activating the Dll4-Notch-Hey2 signaling pathway, HGF indirectly promotes the proliferation and migration ability of cells, so that offspring artery branches are formed.
authors.affiliation: Department of Laboratory Diagnosis, Central Hospital of Xianyang, Xianyang, Shaanxi 712000, China.
authors.forename: Yu-Fang
authors.initials: YF
authors.lastname: Gao
authors.forename: Xiao-Qin
authors.initials: XQ
authors.lastname: Ha
authors.forename: Tong-de
authors.initials: TD
authors.lastname: Lü
authors.forename: Juan-Ping
authors.initials: JP
authors.lastname: Han
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D002135:Calcium-Binding Proteins; D002460:Cell Line; D004797:Enzyme-Linked Immunosorbent Assay; D017228:Hepatocyte Growth Factor / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D051880:Receptors, Notch / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051792:Basic Helix-Loop-Helix Proteins; D002135:Calcium-Binding Proteins; D017228:Hepatocyte Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D051880:Receptors, Notch; D012097:Repressor Proteins; C424126:DLL4 protein, human; C405693:HEY2 protein, human