Escola Paulista de Medicina
Postgraduate Program in Nephrology

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

ppclinsci 132 12and13 cover

Authors: Magaiver Andrade-SilvaMarcos Antonio CenedezeLuiz Augusto PerandiniRaphael José Ferreira FelizardoIngrid Kazue Mizuno WatanabeJuan Sebastian Henao AgudeloAngela CastoldiGiselle Martins GonçalvesClarice Silvia Taemi OrigassaPatricia SemedoMeire Ioshie HiyaneOrestes Foresto-NetoDenise Maria Avancini Costa MalheirosMarlene Antonia ReisClarice Kazue FujiharaRoberto ZatzAlvaro Pacheco-SilvaNiels Olsen Saraiva CâmaraDanilo Candido de Almeida.

Abstract

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.

DOI: 10.1042/CS20170262

 

 

Artigos Relacionados - Artigos Científicos

16 May 2019 12:37

Requiao-Moura LR1, de Sandes-Freitas TV2, Marcelo-Gomes G3, Rangel EB1,3.

Artigos Cientificos
16 May 2019 10:04

[Article in English, Portuguese; Abstract available in Portuguese from the publisher]
Carlotto JRM1, [ ... ]

Artigos Cientificos
16 May 2019 11:35

Rangel EB1,2,3, Gomes SA4,5, Kanashiro-Takeuchi R4,6, Saltzman RG4, Wei C7, Ruiz P8, Reiser J7, Hare [ ... ]

Artigos Cientificos

© 2013 - 2019 Universidade Federal de São Paulo - Unifesp

Rua Botucatu, 591 - 15º andar - Cj 153 - Vila Clementino - São Paulo/SP - 04023-062 • nefrologia@unifesp.br