Platelets are circulating cells that respond to vascular disorders, adhering to endothelial substructures and also physically interact with other platelet, leukocytes and endothelial cells by adhesion receptors expressed on their surfaces. Platelets secrete chemotactic agents, growth factors and fibrinogen, stimulating tissue remodeling after injury through mechanisms involving cell migration, proliferation and matrix synthesis. In renal pathologies, the role of platelets is still restricted to observations and associations without exposing its real mechanism of action. In this project, we hypothesized that platelets not only participate in the process of tissue remodeling after injury, as well as acting as effectors in the injury, because of its role in adhesion and cell signaling mechanisms. So we aimed to evaluate platelet participation in an experimental model of glomerulonephritis (GN), via the bifunctional inhibitor of integrins (Insularin) action in both endothelial cells and platelets. For this purpose, C57BL/6 mice are submitted to administration of the serum anti-GBM and treated or not with insularin. Animals will be sacrificed over 1, 4, 7 and 9 days, corresponding to the acute and chronic phases of injury. The presence of platelets during different phases of the lesion will be seen by immunohistochemical and western blot analysis. Renal dysfunction will be analyzed by biochemical, gene and protein expression of markers of aggression/tissue protection in renal tissue. After verifying that platelets are involved in experimental GN, we seek to study the mechanism using an in vitro model of platelet-endothelial-mesangial cells interaction in an attempt to reproduce the phenomena in vivo. The development of a new therapy for GN could involve the neutralization of platelet function in order to mitigate the glomerular lesions and hence slow the progression of chronic renal disease.
News published in Agência FAPESP Newsletter about the scholarship: