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Angiogenesis and growth factor modulation induced by alternagin C, a snake venom disintegrin-like, cysteine-rich protein on a rat skin wound model
Authors:Sant'Ana Estela Maria Correia  Gouvêa Cibele Marli Cação Paiva  Nakaie Clóvis Ryuichi  Selistre-de-Araújo Heloisa Sobreiro
Affiliation:a Departamento de Ciências Fisiológicas, Universidade Federal de São Carlos, Rodovia Washington Luís, km 235, São Carlos 13565-905, SP, Brazil
b Departamento de Ciências Biológicas, Universidade Federal de Alfenas, Rua Gabriel Monteiro da Silva, 714, Alfenas 37130-000, MG, Brazil
c Departamento de Biofísica, Universidade Federal de São Paulo, Rua 3 de maio, 100, São Paulo 04044-020, SP, Brazil
Abstract:In this work, we show that alternagin-C (ALT-C) and ALT-C PEP, a peptide derived from its sequence, were able to induce angiogenesis in wounded rat skin. A spherical cutaneous excision was made in the back of each animal and treated with three different concentrations of ALT-C or ALT-C PEP. After that, the skin was removed and analyzed to verify the presence of new vessels and the expression of growth factors. ALT-C and ALT-C PEP induced the formation of new vessels and modulated the expression of growth factors, mainly VEGF and FGF1. The expression of VEGF increased and it could be detected up to 7 days after injury. FGF1 also significantly increased, but at a lesser extent than VEGF. In conclusion, the present study shows for the first time the stimulation of angiogenesis in an injured tissue by a disintegrin-like protein and that ALT-C may exert this effect by modulating the expression of growth factors.
Keywords:Disintegrin   Snake venom   Growth factors   Alternagin-C   Alpha2beta1 integrin   Bothrops alternatus   Angiogenesis   Skin wound   Rat model   ALT-C PEP   Peptide
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