TLR2 and TLR4 play opposite role in autophagy associated with cisplatin-induced acute kidney injury

Autor(es):Mostrar menos -

Andrade-Silva, Magaiver ^[1] ; Cenedeze, Marcos Antonio ^[2] ; Perandini, Luiz Augusto ^[1] ; Ferreira Felizardo, Raphael Jose ^[1] ; Mizuno Watanabe, Ingrid Kazue ^[2] ; Henao Agudelo, Juan Sebastian ^[2] ; Castoldi, Angela ^[1] ; Goncalves, Giselle Martins ^[1] ; Taemi Origassa, Clarice Silvia ^[2] ; Semedo, Patricia ^[2] ; Hiyane, Meire Ioshie ; Foresto-Neto, Orestes ^[3] ; Avancini Costa Malheiros, Denise Maria ^[4] ; Reis, Marlene Antonia ^[5] ; Fujihara, Clarice Kazue ^[3] ; Zatz, Roberto ; Pacheco-Silva, Alvaro ^[2] ; Saraiva Camara, Niels Olsen ^{[1, 2]} ; de Almeida, Danilo Candido ^{[1, 2]}

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Dept Immunol, Sao Paulo - Brazil

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

^[3] Univ Sao Paulo, Fac Med, Dept Clin Med, Renal Div, Sao Paulo - Brazil

^[4] Univ Sao Paulo, Dept Med, Renal Pathol, Sao Paulo - Brazil

^[5] Univ Fed Triangulo Mineiro, Dept Biomed Sci, Uberaba - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Clinical Science; v. 132, n. 16, p. 1725-1739, AUG 31 2018.
• Citações Web of Science: 9

Resumo

Acute kidney injury (AKI) is considered an inflammatory disease in which toll-like receptors (TLRs) signaling pathways play an important role. The activation of TLRs results in production of several inflammatory cytokines leading to further renal damage. In contrast, TLRs are key players on autophagy induction, which is associated with a protective function on cisplatin-induced AKI. Hence, the present study aimed to evaluate the specific participation of TLR2 and TLR4 molecules on the development of cisplatin-induced AKI. Complementarily, we also investigated the link between TLRs and heme oxygenase-1 (HO-1), a promisor cytoprotective molecule. First, we observed that only the absence of TLR2 but not TLR4 in mice exacerbated the renal dysfunction, tissue injury and mortality rate, even under an immunologically privileged microenvironment. Second, we demonstrated that TLR2 knockout (KO) mice presented lower expression of autophagy-associated markers when compared with TLR4 KO animals. Similar parameter was confirmed in vitro, using tubular epithelial cells derived from both KO mice. To test the cross-talking between HO-1 and TLRs, hemin (an HO-1 internal inducer) was administrated in cisplatin-treated TLR2 and TLR4 KO mice and it was detected an improvement in the global renal tissue parameters. However, this protection was less evident at TLR2 KO mice. In summary, we documented that TLR2 plays a protective role in cisplatin-induced AKI progression, in part, by a mechanism associated with autophagy up-regulation, considering that its interplay with HO-1 can promote renal tissue recover. (AU)

• Processo FAPESP: 07/07139-3 - Investigando o papel da heme-oxigenase 1 em diferentes processos inflamatórios renais em modelos animais
• Beneficiário: Niels Olsen Saraiva Câmara
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 08/55447-1 - Papel dos NOD-like receptor (NLR) na fisiopatogenia de insuficiência renal aguda (IRA) isquêmica e séptica
• Beneficiário: Giselle Martins Gonçalves
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• 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