Role of short chain fatty acids on experimental focal and segmental glomerulosclerosis

• Grant number: 12/15205-4
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: October 01, 2012
• End date: July 31, 2017
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Niels Olsen Saraiva Câmara
• Grantee: Raphael Jose Ferreira Felizardo
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated research grant: 12/02270-2 - New cellular, molecular and immunological mechanisms involved in acute and chronic renal injury: the search for new therapeutical approaches, AP.TEM
• Associated scholarship(s): 14/13135-4 - The role of metabolite-sensing receptors- (GPR41, GPR43 and GPR109A) and epigenetic pathways for the progression of nephropathy, BE.EP.DD

Abstract

Focal and segmental glomerulosclerosis (FSGS) is one of the most important causes of chronic renal diseases thatarisedue to its high prevalence index. Is characterized by proteinuria and histopathological findings, like vascular collapse, mesangial sclerosis and progressive glomerular deterioration, however, the main characteristic of the disease is the podocyte foot processes effacement. The role of short-chain fatty acids (SCFAs) as potential anti-inflammatory and antifibrotic agents in several organs and tissues has been described but their effect on the progression of renal diseases is unknown. SCAFs are produced by intestinal microbiota through anaerobic fermentation of non-digestible dietary residues of carbohydrates and proteins. Our hypothesis turns around the SCFAs modulatory effect on inflammatory process developed during FSGS progression. We intend to evaluate FSGS markers such as podocyte related molecules and inflammatory markers, and thus, evaluate epigenetics data, which has not been explored in nephropathies. Experimental FSGS mimics classics signs of human disease and in this study will be induced in Balb/c mice through a single intravenous injection of Adriamycin (ADM). A group of animals will, afterwards, be treated with SCAFs, in order to evaluate its anti-inflammatory properties. Preliminary results showed that early SCFAs treatment in Balb/c mice submitted to ADM nephropathy reduces the levels of urinary proteins like albumin. The expressions of podocyte related molecules were significantly re-established in animals treated with SCFAs and they furthermore showed lower expression of profibrotic markers. This result suggest that the use of SCFAs can be an alternative tool for the treatment of this renal disease with elevated numbers of mortality and morbidity. (AU)

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)

FELIZARDO, RAPHAEL J. F.; DE ALMEIDA, DANILO C.; PEREIRA, RAFAEL L.; WATANABE, INGRID K. M.; DOIMO, NAYARA T. S.; RIBEIRO, WILLIAN R.; CENEDEZE, MARCOS A.; HIYANE, MEIRE I.; AMANO, MARIANE T.; BRAGA, TARCIO T.; et al. Gut microbial metabolite butyrate protects against proteinuric kidney disease through epigenetic- and GPR109a-mediated mechanisms. FASEB JOURNAL, v. 33, n. 11, p. 11894-11908, NOV 2019. (14/13135-4, 12/02270-2, 12/15205-4, 12/50410-8, 17/05264-7)

FELIZARDO, R. J. F.; WATANABE, I. K. M.; DARDI, PATRIZIA; ROSSONI, L. V.; CAMARA, N. O. S.. The interplay among gut microbiota, hypertension and kidney diseases: The role of short-chain fatty acids. PHARMACOLOGICAL RESEARCH, v. 141, p. 366-377, MAR 2019. (12/15205-4, 17/06222-6, 17/05264-7, 12/02270-2, 16/08907-3)

FERREIRA FELIZARDO, RAPHAEL JOSE; CASTOLDI, ANGELA; ANDRADE-OLIVEIRA, VINICIUS; SARAIVA CAMARA, NIELS OLSEN. The microbiota and chronic kidney diseases: a double-edged sword. CLINICAL & TRANSLATIONAL IMMUNOLOGY, v. 5, JUN 2016. (12/15205-4, 15/18121-4)