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Effect of glomerular barrier dysfunction on proximal tubular cell innate immunity

Grant number: 13/11929-0
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): October 01, 2013
Effective date (End): January 31, 2018
Field of knowledge:Health Sciences - Medicine - Medical Clinics
Principal researcher:Clarice Kazue Fujihara
Grantee:Viviane Dias Faustino
Home Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated research grant:12/10926-5 - Pathogenesis and treatment of chronic kidney disease: role of innate immunity in glomerular, tubular and interstitial injury, AP.TEM


Chronic Kidney Disease involves the participation of several inflammatory events that culminate in renal interstitial fibrosis, even when the process has in the glomeruli. Preventing the progression of chronic nephropathies is one of the greatest challenges faced by nephrologists. Proteinuria correlates with the rate of progression, particularly in glomerulopathies, as well as with the extent of glomerular injury and interstitial inflammation. According to one of the hypotheses proposed to explain this correlation, excessive passage of proteins through the glomerular barrier exerts a toxic effect on proximal tubular cells, which in turn synthesize large amounts of inflammatory mediators. However, the mechanisms that lead to this purported effect are unclear. The aim of the present project is to verify the hypothesis that this intense reabsorption and hydrolysis of proteins leads to stimulation of innate immunity in proximal cells, thus activating inflammatory cascades. To accomplish this goal, we will examine, at various stages of evolution, the adriamycin nephropathy model, which is characterized by massive proteinuria and, in the long run, glomerular and interstitial injury. As an in vitro counterpart, a preparation of cultured cells will be exposed to different concentrations of albumin. If this hypothesis is correct, activation of innate immunity will occur upon exposure to high protein concentrations, thus contributing to clarify the mechanisms of interstitial injury in proteinuric states and helping to define potential new therapeutic targets.

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
FAUSTINO, VIVIANE DIAS; ALARCON ARIAS, SIMONE COSTA; AVILA, VICTOR FERREIRA; FORESTO-NETO, ORESTES; FREGNAN ZAMBOM, FERNANDA FLORENCIA; MACHADO, FLAVIA GOMES; DOS REIS, LUCIENE MACHADO; MARIA, DENISE; MALHEIROS, AVANCINI COSTA; VOLPINI, RILDO APARECIDO; et al. Simultaneous activation of innate and adaptive immunity participates in the development of renal injury in a model of heavy proteinuria. BIOSCIENCE REPORTS, v. 38, n. 4, . (13/11929-0, 12/10926-5)
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
FAUSTINO, Viviane Dias. Effect of dysfunction acute barrier glomerular on the innate immunity of proximal tubular cells. 2018. Doctoral Thesis - Universidade de São Paulo (USP). Faculdade de Medicina (FM/SBD) São Paulo.

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