Gut Bacteria Products Prevent AKI Induced by Ischemia-Reperfusion

Autor(es):Mostrar menos -

Andrade-Oliveira, Vinicius ^[1] ; Amano, Mariane T. ^[1] ; Correa-Costa, Matheus ^[1] ; Castoldi, Angela ^[1] ; Felizardo, Raphael J. F. ^[2] ; de Almeida, Danilo C. ^[2] ; Bassi, Enio J. ^[1] ; Moraes-Vieira, Pedro M. ^[1] ; Hiyane, Meire I. ^[1] ; Rodas, Andrea C. D. ^[1] ; Peron, Jean P. S. ^[3] ; Aguiar, Cristhiane F. ^[1] ; Reis, Marlene A. ^[4] ; Ribeiro, Willian R. ^[5] ; Valduga, Claudete J. ^[5] ; Curi, Rui ^[6] ; Ramirez Vinolo, Marco Aurelio ^[7] ; Ferreira, Caroline M. ^[6] ; Saraiva Camara, Niels Olsen ^{[2, 1]}

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Lab Transplantat Immunobiol, Dept Immunol, Inst Biomed Sci 4, BR-05508000 Sao Paulo - Brazil

^[2] Univ Fed Sao Paulo, Div Nephrol, Sao Paulo - Brazil

^[3] Univ Sao Paulo, Neuroimmune Interact Lab, Dept Immunol, Inst Biomed Sci 4, BR-05508000 Sao Paulo - Brazil

^[4] Univ Fed Triangulo Mineiro, Dept Pathol, Uberaba - Brazil

^[5] Univ Anhanguera Sao Paulo UNIAN SP, Dept Pharm & Biotechnol, Sao Paulo - Brazil

^[6] Univ Sao Paulo, Dept Physiol & Biophys, Inst Biomed Sci 4, BR-05508000 Sao Paulo - Brazil

^[7] Univ Campinas UNICAMP, Inst Biol, Dept Genet Evolut & Bioagents, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY; v. 26, n. 8, p. 1877-1888, AUG 2015.
• Citações Web of Science: 86

Resumo

Short-chain fatty acids (SCFAs) are fermentation end products produced by the intestinal nnicrobiota and have anti-inflammatory and histone deacetylase inhibiting properties. Recently, a dual relationship between the intestine and kidneys has been unraveled. Therefore, we evaluated the role of SCFA in an AKI model in which the inflammatory process has a detrimental role. We observed that therapy with the three main SCFAs (acetate, propionate, and butyrate) improved renal dysfunction caused by injury. This protection was associated with low levels of local and systemic inflammation, oxidative cellular stress, cell infiltration/activation, and apoptosis. However, it was also associated with an increase in autophagy. Moreover, SCFAs inhibited histone deacetylase activity and modulated the expression levels of enzymes involved in chromatin modification. In vitro analyses showed that SCFAs modulated the inflammatory process, decreasing the maturation of dendritic cells and inhibiting the capacity of these cells to induce CD4(+) and CD8(+) T cell proliferation. Furthermore, SCFAs ameliorated the effects of hypoxia in kidney epithelial cells by improving mitochondria! biogenesis. Notably, mice treated with acetate-producing bacteria also had better outcomes after AKI. Thus, we demonstrate that SCFAs improve organ function and viability after an injury through modulation of the inflammatory process, most likely via epigenetic modification. (AU)

• Processo FAPESP: 12/02270-2 - Novos mecanismos celulares, moleculares e imunológicos das lesões renais agudas e crônicas: busca por novas estratégias terapêuticas
• Beneficiário: Niels Olsen Saraiva Câmara
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 11/01016-2 - Ácidos Graxos de Cadeia Curta (SCFA) como moduladores da resposta inflamatória na lesão renal aguda e crônica experimental
• Beneficiário: Vinicius de Andrade Oliveira
• Modalidade de apoio: Bolsas no Brasil - Doutorado