title: H-RN, a peptide derived from hepatocyte growth factor, inhibits corneal neovascularization by inducing endothelial apoptosis and arresting the cell cycle.
abstract: BACKGROUND
  The goal of this study was to investigate the anti-angiogenic activity of a novel peptide H-RN, derived from the hepatocyte growth factor kringle 1 domain (HGF K1), in a mouse model of corneal neovascularization. The anti-angiogenic effect of H-RN on vascular endothelial growth factor (VEGF)-stimulated cell proliferation, cell migration and endothelial cell tube formation was assessed in vitro using Human Umbilical Vein Endothelial Cells (HUVECs) and in vivo using a mouse cornea micropocket assay. Apoptosis and cell cycle arrest were assessed by flow cytometry. A scrambled peptide was used as a negative control.
  
  
  RESULTS
  H-RN effectively inhibited VEGF-stimulated HUVEC proliferation, migration and tube formation on Matrigel, while a scrambled peptide exerted no effect. In the mouse model of corneal angiogenesis, VEGF-stimulated angiogenesis was significantly inhibited by H-RN compared to a scrambled peptide that had no such activity. VEGF protected HUVECs from apoptosis, while H-RN inhibited this protective effect of VEGF. VEGF significantly increased the proportion of cells in the S phase compared to control treated cells (p<0.05). Treatment with H-RN (1.5 mM) induced the accumulation of cells in G0/G1 phase, while the proportion of cells in the S phase and G2/M phase decreased significantly compared to control group (p<0.05).
  
  
  CONCLUSIONS
  H-RN has anti-angiogenic activity in HUVECs and in a mouse model of VEGF-induced corneal neovascularization. The anti-angiogenic activity of H-RN was related to apoptosis and cell cycle arrest, indicating a potential strategy for anti-angiogenic treatment in the cornea.
authors: Department of Biology, Shanghai Institute of Technology, Shanghai 200235, PR China.
authors: Ye
authors: Y
authors: Sun
authors: Li
authors: L
authors: Su
authors: Zhongxiao
authors: Z
authors: Wang
authors: Yi
authors: Y
authors: Xu
authors: Xun
authors: X
authors: Xu
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D003094:Collagen / Q000737:chemistry; D003315:Cornea / Q000098:blood supply; D016510:Corneal Neovascularization / Q000188:drug therapy; D004195:Disease Models, Animal; D004338:Drug Combinations; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects*; D017228:Hepatocyte Growth Factor / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007797:Laminin / Q000737:chemistry; D051379:Mice; D009389:Neovascularization, Pathologic; D010446:Peptide Fragments / Q000494:pharmacology* / Q000627:therapeutic use; D017434:Protein Structure, Tertiary; D011509:Proteoglycans / Q000737:chemistry; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology
chemical_list: D020533:Angiogenesis Inhibitors; D004338:Drug Combinations; C581855:H-RN peptide; D007797:Laminin; D010446:Peptide Fragments; D011509:Proteoglycans; D042461:Vascular Endothelial Growth Factor A; C059485:matrigel; D017228:Hepatocyte Growth Factor; D003094:Collagen