Please use this identifier to cite or link to this item: https://observatorio.fm.usp.br/handle/OPI/35707
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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.date.accessioned2020-03-24T15:00:30Z
dc.date.available2020-03-24T15:00:30Z
dc.date.issued2019
dc.identifier.citationFASEB JOURNAL, v.33, n.11, p.11894-11908, 2019
dc.identifier.issn0892-6638
dc.identifier.urihttps://observatorio.fm.usp.br/handle/OPI/35707
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.language.isoeng
dc.publisherFEDERATION AMER SOC EXP BIOLeng
dc.relation.ispartofFaseb Journal
dc.rightsrestrictedAccesseng
dc.subjectglomerulopathyeng
dc.subjectpodocyteeng
dc.subjectADR nephropathyeng
dc.subjectSCFAeng
dc.subject.otherchain fatty-acidseng
dc.subject.otherdietary fibereng
dc.subject.othersodium-butyrateeng
dc.subject.otherinflammationeng
dc.subject.otherreceptoreng
dc.subject.otheractivationeng
dc.subject.otherglomerulosclerosiseng
dc.subject.otheracetylationeng
dc.subject.otherprogressioneng
dc.subject.otherexpressioneng
dc.titleGut microbial metabolite butyrate protects against proteinuric kidney disease through epigenetic- and GPR109a-mediated mechanismseng
dc.typearticleeng
dc.rights.holderCopyright FEDERATION AMER SOC EXP BIOLeng
dc.identifier.doi10.1096/fj.201901080R
dc.identifier.pmid31366236
dc.subject.wosBiochemistry & Molecular Biologyeng
dc.subject.wosBiologyeng
dc.subject.wosCell Biologyeng
dc.type.categoryoriginal articleeng
dc.type.versionpublishedVersioneng
hcfmusp.author.externalFELIZARDO, Raphael J. F.:Univ Fed Sao Paulo, Dept Med, Nephrol Div, Sao Paulo, Brazil; Univ Sao Paulo, Fac Med, Inst Biomed Sci 4, Dept Immunol, Sao Paulo, Brazil; Monash Univ, Dept Biochem & Mol Biol, Biodiscovery Inst, Clayton, Vic, Australia
hcfmusp.author.externalALMEIDA, Danilo C. de:Univ Fed Sao Paulo, Dept Med, Nephrol Div, Sao Paulo, Brazil; Univ Sao Paulo, Fac Med, Inst Biomed Sci 4, Dept Immunol, Sao Paulo, Brazil
hcfmusp.author.externalPEREIRA, Rafael L.:Univ Fed Parana, Dept Physiol, Curitiba, Parana, Brazil
hcfmusp.author.externalWATANABE, Ingrid K. M.:Univ Fed Sao Paulo, Dept Med, Nephrol Div, Sao Paulo, Brazil; Univ Sao Paulo, Fac Med, Inst Biomed Sci 4, Dept Immunol, Sao Paulo, Brazil
hcfmusp.author.externalDOIMO, Nayara T. S.:Hosp Sirio Liban es, Ctr Mol Oncol, Sao Paulo, Brazil
hcfmusp.author.externalRIBEIRO, Willian R.:Univ Fed Sao Paulo, Inst Environm Chem & Pharmaceut Sci, Dept Pharmaceut Sci, Diadema, Brazil
hcfmusp.author.externalCENEDEZE, Marcos A.:Univ Fed Sao Paulo, Dept Med, Nephrol Div, Sao Paulo, Brazil
hcfmusp.author.externalHIYANE, Meire I.:Univ Sao Paulo, Fac Med, Inst Biomed Sci 4, Dept Immunol, Sao Paulo, Brazil
hcfmusp.author.externalAMANO, Mariane T.:Univ Sao Paulo, Fac Med, Inst Biomed Sci 4, Dept Immunol, Sao Paulo, Brazil; Hosp Sirio Liban es, Ctr Mol Oncol, Sao Paulo, Brazil
hcfmusp.author.externalBRAGA, Tarcio T.:Univ Sao Paulo, Fac Med, Inst Biomed Sci 4, Dept Immunol, Sao Paulo, Brazil
hcfmusp.author.externalFERREIRA, Caroline M.:Univ Fed Sao Paulo, Inst Environm Chem & Pharmaceut Sci, Dept Pharmaceut Sci, Diadema, Brazil
hcfmusp.author.externalPARMIGIANI, Raphael B.:Idengene Med Diagnost, Sao Paulo, Brazil
hcfmusp.author.externalANDRADE-OLIVEIRA, Vinicius:Univ Sao Paulo, Fac Med, Inst Biomed Sci 4, Dept Immunol, Sao Paulo, Brazil
hcfmusp.author.externalVINOLO, Marco Aurelio R.:Univ Estadual Campinas, Inst Biol, Dept Genet Evolut Microbiol & Immunol, Campinas, Brazil
hcfmusp.author.externalMARINO, Eliana:Monash Univ, Dept Biochem & Mol Biol, Biodiscovery Inst, Clayton, Vic, Australia
hcfmusp.author.externalROBERT, Remy:Monash Univ, Dept Biochem & Mol Biol, Biodiscovery Inst, Clayton, Vic, Australia
hcfmusp.author.externalMACKAY, Charles R.:Monash Univ, Dept Biochem & Mol Biol, Biodiscovery Inst, Clayton, Vic, Australia
hcfmusp.description.beginpage11894
hcfmusp.description.endpage11908
hcfmusp.description.issue11
hcfmusp.description.volume33
hcfmusp.origemWOS
hcfmusp.origem.idWOS:000507461600025
hcfmusp.origem.id2-s2.0-85074378236
hcfmusp.publisher.cityBETHESDAeng
hcfmusp.publisher.countryUSAeng
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dc.description.indexMEDLINEeng
dc.identifier.eissn1530-6860
hcfmusp.citation.scopus32
hcfmusp.scopus.lastupdate2022-06-03-
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