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Open Access Research article

H-RN, a peptide derived from hepatocyte growth factor, inhibits corneal neovascularization by inducing endothelial apoptosis and arresting the cell cycle

Ye Sun1, Li Su2, Zhongxiao Wang2, Yi Xu2* and Xun Xu2

Author Affiliations

1 Department of Biology, Shanghai Institute of Technology, 200235, Shanghai, P.R. China

2 Department of Ophthalmology, Shanghai First People’s Hospital, Shanghai JiaoTong University, Haining Road 100, 200080, Shanghai, P.R. China

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BMC Cell Biology 2013, 14:8  doi:10.1186/1471-2121-14-8

Published: 24 February 2013

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.

Keywords:
H-RN; Peptide; HUVECs; Cornea; Neovascularization