The incidence of progressive chronic kidney disease has grown considerably in recent decades. In Brazil, in 2006 it was spent U.S. $ 1.4 billion to treat patients on chronic dialysis and renal transplantation. There are 32,375 new patients estimated with end stage renal disease a year in Brazil. The tubule-interstitial fibrosis is a major event of chronic kidney disease and is also an important predictor of renal dysfunction. The fibrous tissue is caused by the accumulation of fibroblasts, myofibroblasts and extracellular matrix. Despite the controversies, myofibroblasts can be derived from resident fibroblasts and fibroblasts can be derived from renal epithelial cells. Recently, another factor was added to this complex system: fibroblasts can also be derived from endothelial cells by the process of endothelial to mesenchymal transition (EndMT). The EndMT is a process in which the renal endothelial cells lose their phenotypic characteristics and acquire features of mesenchymal cells, providing a rich and renewable source of myofibroblasts. The recent discoveries of EndMT in different diseases suggest that the modulation EndMT may represent a promising treatment to delay progression of the disease. It has been demonstrated in epithelial-to-mesenchymal transition (EMT) that the heme oxygenase-1, endogenous enzyme, can suppress an acute renal injury and even halt a renal fibrosis through inhibition of the infiltration of inflammatory cells, due to its antioxidant, anti-inflammatory and anti-apoptotic, seen in experimental models in vivo and in vitro. In this project, we intend to evaluate and characterize the properties of mesenchymal cells derived from endothelial cells as an expression of surface markers and the ability to produce collagen in different models of renal injury in vivo and in vitro. Moreover, we intend to modulate the EndMT with the use of drugs that induce HO-1 by overexpression or gene silencing of their RNA. Thus, we not only identify the mechanisms that lead to an endothelial cell to gain mesenchymal markers as well as develop new tools to control the fibrotic process.
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