New cellular, molecular and immunological mechanisms involved in acute and chronic renal injury: the search for new therapeutical approaches

Abstract

In recent years, several research groups in Brazil and abroad, including ours, have consistently shown the role of the inflammatory response in some kidney diseases. Despite the advances have been most prominent in animal models, the strongly generated data indicate that acute and chronic renal lesions are influenced by the immune response, up to now considered sterile in all compartments of the nephron. Now considered an epidemic, renal diseases have enormous social and economic impact with high morbidity and mortality for patients. Thus, acquisition of new knowledge will strengthen the knowledge about the pathogenesis of these diseases, and discovery of new strategies to improve renal dysfunction become necessary to improve patient survival. Specifically, the results obtained by our group in these years show that both components of the innate immune response, such as endothelial cells, cyclooxygenase, bradykinin, and the elements of the adaptive immune response, such as CD4 + T lymphocytes, receptors of innate immunity (like Toll like receptors and Nod-like) and cells participate as effectors of renal injury. We also saw that early after the begging of an inflammatory response, the renal tissue is able to mount a cytoprotective response ranging from a reorganization of the expression of proteins in the endoplasmic reticulum to the action of HO-1. More recently, new molecules, hormones and cell subsets were identified and shown to participate in various inflammatory diseases. With changes in lifestyle, new factors were added to the list of co-morbidities renal diseases such as obesity. Along with these, new adipogenicity related hormones; changes in intestinal microflora and inflammatory molecules have been given an important role in the pathogenesis of renal injury. In this project, we intend to further study the participation of the inflammatory response in renal lesions, with a current text, taking into account new molecules, lymphocyte/macrophages subsets and molecules with new functions in different models of acute and chronic kidney injury and models of cell injury "in vitro". We intend to respond to a working hypothesis and objectives. (AU)