Subprojeto 9 – Integrins and disintegrins: identification of snake venoms components with angiogenic potential
Participante: Heloisa Sobreiro Selistre de Araújo (UFSCar)
Integrins are cell surface receptors for extracellular matrix components. These receptors mediate the adhesion of cells to their microenvironment. Integrin binding triggers intracellular signaling pathways that result in cell survival, migration and proliferation, and they have been suggested as important targets for the treatment of several diseases such as thrombosis and cancer. Disintegrins are integrin-ligand molecules that were first isolated from snake venoms. The structural diversity of these proteins, mostly due to the presence of distinct adhesive motifs, results in binding to specific integrins. Therefore disintegrins have been suggested as potential candidates for drug design targeting the integrins. Our research project focuses the application of native and recombinant disintegrins in therapeutical angiogenesis. Purified disintegrins are tested in both in vitro and in vivo assays and modulation of cellular activities are followed by different methods, including confocal microscopy, exploring different extracellular matrix components by the use of SHG (for collagen) and autofluorescence (for elastin). Furthermore, the effect of these molecules will be analysed on isolated endothelial cells in culture, following several parameters of cell physiology.