The role of metabolite-sensing receptors- (GPR41, GPR43 and GPR109A) and epigenetic pathways for the progression of nephropathy

• Grant number: 14/13135-4
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate (Direct)
• Effective date (Start): December 15, 2014
• Effective date (End): December 14, 2015
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Niels Olsen Saraiva Câmara
• Grantee: Raphael Jose Ferreira Felizardo
• Supervisor: Charles Mackay
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Research place: Monash University, Australia
• Associated to the scholarship: 12/15205-4 - Role of short chain fatty acids on experimental focal and segmental glomerulosclerosis, BP.DD

Abstract

Short chain fatty acids (SCFAs) are metabolites produced by intestinal microbes upon digestion of dietary fibre. SCFAs show a range of effects on the immune system, and are involved in several inflammatory processes. In particular, SCFAs have been associated with gut homeostasis, for instance by regulating Treg cell numbers, macrophage activation, epithelial integrity and enterocyte functions. These effects are attributed to activation of metabolite-sensing receptors GPR41, GPR43 and GPR109 and also to induction of epigenetic modification in histones, particularly inhibition of histone deacetylases. Although emerging data have shown that SCFAs modulate immune responses, there are no studies in the context of renal disease. In light of recent findings, we expect that SCFAs once absorbed into the circulation could affect kidney biology, by activating metabolite-sensing receptors and thus modulating renal inflammatory injury. At the same time, SCFAs could inhibit HDACs and alter epigenetically the transcription of specific genes in infiltrating and parenchymal renal cells. In this study, we propose to investigate how these receptors are involved in renal diseases and the role of SCFAs in inhibiting HDACs in order to alter gene transcription in effector cells. (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)