Abstract
The inflammatory and hormonal mechanisms involved in acute kidney injury (AKI) have been, recently, the focus of intense research, because the new methodologies and better understanding of this complex pathophysiological entity indicate that such issues are central to the advancement of knowledge and potential clinical interventions. This project aims to evaluate, using different complementary strategies, the factors involved in AKI. These strategies are as follows. First, we will evaluate cell signaling pathways related to apoptosis in human mesangial cells immortalized with LPS and uric acid, both of which are known to stimulate various inflammatory and vasoactive substances. Second, given that the number of stem cell studies has shown explosive growth, because, in experimental terms, various results stimulate the search for pathophysiological mechanisms, especially paracrine hormonal events involved in the administration of these cells, our lab has developed projects using mesenchymal stem cells in several models of AKI, such as gentamicin, cyclosporine and acyclovir nephrotoxicity, as well as sepsis induced by LPS and by inoculation of nephritogenic Escherichia coli. Preliminary results are quite indicative of paracrine events, requiring the evaluation and measurement of various inflammatory and anti-inflammatory substances. Third, because, in the specific field of renal diseases, the effects of mesenchymal stem cells have been studied most intensely, and yet there are experimental findings of significant effects of endothelial progenitor stem cells (predominantly angiogenic) and stem cells derived from adipose tissue, we have cultured these cells which, together with mesenchymal cells and hematopoietic cells, constitute a bank of stem cells, which we will make available to the scientific community as well as to test the pathophysiological mechanisms in order to identify the best cell line or cell line mixture. Fourth, in that same line of research (inflammatory mechanisms), we have studied induced AKI in animals and in kidney cells of Chagas disease in vitro, in which the inflammatory process is very intense, involving cytokines and pro and anti-inflammatory factors. All of these projects will benefit from the acquisition of the equipment requested. (AU)