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dc.contributorSistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSP
dc.contributor.authorFELIZARDO, Raphael J. F.
dc.contributor.authorALMEIDA, Danilo C. de
dc.contributor.authorPEREIRA, Rafael L.
dc.contributor.authorWATANABE, Ingrid K. M.
dc.contributor.authorDOIMO, Nayara T. S.
dc.contributor.authorRIBEIRO, Willian R.
dc.contributor.authorCENEDEZE, Marcos A.
dc.contributor.authorHIYANE, Meire I.
dc.contributor.authorAMANO, Mariane T.
dc.contributor.authorBRAGA, Tarcio T.
dc.contributor.authorFERREIRA, Caroline M.
dc.contributor.authorPARMIGIANI, Raphael B.
dc.contributor.authorANDRADE-OLIVEIRA, Vinicius
dc.contributor.authorVOLPINI, Rildo A.
dc.contributor.authorVINOLO, Marco Aurelio R.
dc.contributor.authorMARINO, Eliana
dc.contributor.authorROBERT, Remy
dc.contributor.authorMACKAY, Charles R.
dc.contributor.authorCAMARA, Niels O. S.
dc.identifier.citationFASEB JOURNAL, v.33, n.11, p.11894-11908, 2019
dc.description.abstractButyrate is a short-chain fatty acid derived from the metabolism of indigestible carbohydrates by the gut microbiota. Butyrate contributes to gut homeostasis, but it may also control inflammatory responses and host physiology in other tissues. Butyrate inhibits histone deacetylases, thereby affecting gene transcription, and also signals through the metabolite-sensing G protein receptor (GPR)109a. We produced an mAb to mouse GPR109a and found high expression on podocytes in the kidney. Wild-type and Gpr109a(-/-) mice were induced to develop nephropathy by a single injection of Adriamycin and treated with sodium butyrate or high butyrate-releasing high-amylose maize starch diet. Butyrate improved proteinuria by preserving podocyte at glomerular basement membrane and attenuated glomerulosclerosis and tissue inflammation. This protective phenotype was associated with increased podocyte-related proteins and a normalized pattern of acetylation and methylation at promoter sites of genes essential for podocyte function. We found that GPR109a is expressed by podocytes, and the use of Gpr109a(-/-) mice showed that the protective effects of butyrate depended on GPR109a expression. A prebiotic diet that releases high amounts of butyrate also proved highly effective for protection against kidney disease. Butyrate and GPR109a play a role in the pathogenesis of kidney disease and provide one of the important molecular connections between diet, the gut microbiota, and kidney disease.eng
dc.description.sponsorshipFundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [2012/15205-4, 2012/50410-8, 2012/02270-2, 2014/13135-4, 2017/06222-06, 2017/05264-7]
dc.description.sponsorshipConselho Nacional de Desenvolvimento Cientifico e Tecnologico, (CNPq)National Council for Scientific and Technological Development (CNPq)
dc.description.sponsorshipInstituto Nacional de Ciencia e Tecnologia (INCT) REGENERA
dc.description.sponsorshipNational Health and Medical Research Council of AustraliaNational Health and Medical Research Council of Australia
dc.description.sponsorshipCoordenacao de Aperfeicoamento de Pessoal de N'ivel Superior-Brasil (CAPES)CAPES [001]
dc.relation.ispartofFaseb Journal
dc.subjectADR nephropathyeng
dc.subject.otherchain fatty-acidseng
dc.subject.otherdietary fibereng
dc.titleGut microbial metabolite butyrate protects against proteinuric kidney disease through epigenetic- and GPR109a-mediated mechanismseng
dc.rights.holderCopyright FEDERATION AMER SOC EXP BIOLeng
dc.subject.wosBiochemistry & Molecular Biologyeng
dc.subject.wosCell Biologyeng
dc.type.categoryoriginal articleeng
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