|Title:||Aggretin Venom Polypeptide as a Novel Anti-angiogenesis Agent by Targeting Integrin alpha2beta1||Authors:||Chung C.H.
|Issue Date:||2017||Journal Volume:||7||Start page/Pages:||43612||Source:||Scientific Reports||Abstract:||
VEGF and VEGFR antibodies have been used as a therapeutic strategy to inhibit angiogenesis in many diseases; however, frequent and repeated administration of these antibodies to patients induces immunogenicity. In previous studies, we demonstrated that aggretin, a heterodimeric snake venom C-type lectin, exhibits pro-angiogenic activities via integrin α2β1 ligation. We hypothesised that small-mass aggretin fragments may bind integrin α2β1 and act as antagonists of angiogenesis. In this study, the anti-angiogenic efficacy of a synthesised aggretin α-chain C-terminus (AACT, residue 106-136) was evaluated in both in vitro and in vivo angiogenesis models. The AACT demonstrated inhibitory effects on collagen-induced platelet aggregation and HUVEC adhesion to immobilised collagen. These results indicated that AACT may block integrin α2β1-collagen interaction. AACT also inhibited HUVEC migration and tube formation. Aortic ring sprouting and Matrigel implant models demonstrated that AACT markedly inhibited VEGF-induced neovascularisation. In addition, induction of FAK/PI3K/ERK1/2 tyrosine phosphorylation and talin 1/2 associated with integrin β1 which are induced by VEGF were blocked by AACT. Similarly, tyrosine phosphorylation of VEFGR2 and ERK1/2 induced by VEGF was diminished in integrin α2-silenced endothelial cells. Our results demonstrate that AACT is a potential therapeutic candidate for angiogenesis related-diseases via integrin α2β1 blockade. ? 2017 The Author(s).
|URI:||https://scholars.lib.ntu.edu.tw/handle/123456789/564106||ISSN:||20452322||DOI:||10.1038/srep43612||SDG/Keyword:||angiogenesis inhibitor; collagen; focal adhesion kinase 1; laminin; lectin; matrigel; peptide; phosphatidylinositol 3 kinase; protein binding; proteoglycan; PTK2 protein, human; snake venom; vasculotropin A; very late activation antigen 2; angiogenesis; antagonists and inhibitors; cell culture; cell motion; cell proliferation; cell survival; chemistry; drug combination; drug effect; human; metabolism; signal transduction; thrombocyte aggregation; umbilical vein endothelial cell; Angiogenesis Inhibitors; Cell Movement; Cell Proliferation; Cell Survival; Cells, Cultured; Collagen; Drug Combinations; Focal Adhesion Kinase 1; Human Umbilical Vein Endothelial Cells; Humans; Integrin alpha2beta1; Laminin; Lectins, C-Type; Neovascularization, Physiologic; Peptides; Phosphatidylinositol 3-Kinases; Platelet Aggregation; Protein Binding; Proteoglycans; Signal Transduction; Snake Venoms; Vascular Endothelial Growth Factor A
|Appears in Collections:||藥理學科所|
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.