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Title: TLR2 and TLR4 play opposite role in autophagy associated with cisplatin-induced acute kidney injury
Authors: ANDRADE-SILVA, MagaiverCENEDEZE, Marcos AntonioPERANDINI, Luiz AugustoFELIZARDO, Raphael Jose FerreiraWATANABE, Ingrid Kazue MizunoAGUDELO, Juan Sebastian HenaoCASTOLDI, AngelaGONCALVES, Giselle MartinsORIGASSA, Clarice Silvia TaemiSEMEDO, PatriciaHIYANE, Meire IoshieFORESTO-NETO, OrestesMALHEIROS, Denise Maria Avancini CostaREIS, Marlene AntoniaFUJIHARA, Clarice KazueZATZ, RobertoPACHECO-SILVA, AlvaroCAMARA, Niels Olsen SaraivaALMEIDA, Danilo Candido de
Citation: CLINICAL SCIENCE, v.132, n.16, p.1725-1739, 2018
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.
Appears in Collections:

Artigos e Materiais de Revistas Científicas - FM/MCM
Departamento de Clínica Médica - FM/MCM

Artigos e Materiais de Revistas Científicas - FM/MPT
Departamento de Patologia - FM/MPT

Artigos e Materiais de Revistas Científicas - HC/ICHC
Instituto Central - HC/ICHC

Artigos e Materiais de Revistas Científicas - LIM/05
LIM/05 - Laboratório de Poluição Atmosférica Experimental

Artigos e Materiais de Revistas Científicas - LIM/16
LIM/16 - Laboratório de Fisiopatologia Renal

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