Gut microbial metabolite butyrate protects against proteinuric kidney disease through epigenetic‐ and GPR109a‐mediated mechanisms
| Autor: | Willian R. Ribeiro, Mariane Tami Amano, Marcos Antonio Cenedeze, Charles R. Mackay, Caroline M. Ferreira, Rafael Pereira, Vinicius Andrade-Oliveira, Tarcio Teodoro Braga, Danilo Candido de Almeida, Niels Olsen Saraiva Camara, Eliana Mariño, Marco Aurélio Ramirez Vinolo, Meire Ioshie Hiyane, Raphael B. Parmigiani, Remy Robert, Nayara T. S. Doimo, Rildo Aparecido Volpini, Raphael José Ferreira Felizardo, Ingrid Kazue Mizuno Watanabe |
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| Rok vydání: | 2019 |
| Předmět: |
Male
0301 basic medicine Butyrate Gut flora Protective Agents Biochemistry Epigenesis Genetic Receptors G-Protein-Coupled Nephropathy Podocyte 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Genetics medicine Animals Molecular Biology IMUNOLOGIA Cells Cultured Mice Knockout Mice Inbred BALB C Kidney Bacteria biology Podocytes Glomerular basement membrane Glomerulosclerosis Sodium butyrate medicine.disease biology.organism_classification Gastrointestinal Microbiome Cell biology Mice Inbred C57BL Butyrates Proteinuria 030104 developmental biology medicine.anatomical_structure chemistry Kidney Diseases 030217 neurology & neurosurgery Biotechnology |
| Zdroj: | Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual) Universidade de São Paulo (USP) instacron:USP |
| Popis: | Butyrate 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.-Felizardo, R. J. F., de Almeida, D. C., Pereira, R. L., Watanabe, I. K. M., Doimo, N. T. S., Ribeiro, W. R., Cenedeze, M. A., Hiyane, M. I., Amano, M. T., Braga, T. T., Ferreira, C. M., Parmigiani, R. B., Andrade-Oliveira, V., Volpini, R. A., Vinolo, M. A. R., Marino, E., Robert, R., Mackay, C. R., Camara, N. O. S. Gut microbial metabolite butyrate protects against proteinuric kidney disease through epigenetic- and GPR109a-mediated mechanisms. |
| Databáze: | OpenAIRE |
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