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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 <jats:italic>in vitro<\/jats:italic> using Human Umbilical Vein Endothelial Cells (HUVECs) and <jats:italic>in vivo<\/jats:italic> 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.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>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 (<jats:italic>p<\/jats:italic>&lt;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 (<jats:italic>p<\/jats:italic>&lt;0.05).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>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.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1471-2121-14-8","type":"journal-article","created":{"date-parts":[[2013,2,24]],"date-time":"2013-02-24T15:14:00Z","timestamp":1361718840000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["H-RN, a peptide derived from hepatocyte growth factor, inhibits corneal neovascularization by inducing endothelial apoptosis and arresting the cell cycle"],"prefix":"10.1186","volume":"14","author":[{"given":"Ye","family":"Sun","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Su","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhongxiao","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xun","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2013,2,24]]},"reference":[{"key":"645_CR1","doi-asserted-by":"publisher","first-page":"799","DOI":"10.1016\/j.micinf.2005.03.003","volume":"7","author":"PS Biswas","year":"2005","unstructured":"Biswas PS, Rouse BT: Early events in HSV keratitis\u2013setting the stage for a blinding disease. 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