title: Role of NLRP3 Inflammasomes for Rhabdomyolysis-induced Acute Kidney Injury.
abstract: Rhabdomyolysis is one of the main causes of community-acquired acute kidney injury (AKI). Although inflammation is involved in the pathogenesis of rhabdomyolysis-induced AKI (RIAKI), little is known about the mechanism that triggers inflammation during RIAKI. Recent evidence has indicated that sterile inflammation triggered by tissue injury can be mediated through multiprotein complexes called the inflammasomes. Therefore, we investigated the role of NLRP3 inflammasomes in the pathogenesis of RIAKI using a glycerol-induced murine rhabdomyolysis model. Inflammasome-related molecules were upregulated in the kidney of RIAKI. Renal tubular injury and dysfunction preceded leukocyte infiltration into the kidney during the early phase of RIAKI, and they were markedly attenuated in mice deficient in NLRP3, ASC, caspase-1, and interleukin (IL)-1β compared with those in wild-type mice. No difference in leukocyte infiltration was observed between wild-type and NLRP3-deficient mice. Furthermore, NLRP3 deficiency strikingly suppressed the expression of renal injury markers and inflammatory cytokines and apoptosis of renal tubular cells. These results demonstrated that NLRP3 inflammasomes contribute to inflammation, apoptosis, and tissue injury during the early phase of RIAKI and provide new insights into the mechanism underlying the pathogenesis of RIAKI.
authors.affiliation: 1] Division of Inflammation Research, Center for Molecular Medicine [2] Department of Nephrology, Jichi Medical University, Tochigi.
authors.forename: Takanori
authors.initials: T
authors.lastname: Komada
authors.affiliation: Division of Inflammation Research, Center for Molecular Medicine.
authors.forename: Fumitake
authors.initials: F
authors.lastname: Usui
authors.affiliation: Division of Inflammation Research, Center for Molecular Medicine.
authors.forename: Akira
authors.initials: A
authors.lastname: Kawashima
authors.affiliation: Division of Inflammation Research, Center for Molecular Medicine.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Kimura
authors.affiliation: Division of Inflammation Research, Center for Molecular Medicine.
authors.forename: Tadayoshi
authors.initials: T
authors.lastname: Karasawa
authors.affiliation: Division of Inflammation Research, Center for Molecular Medicine.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Inoue
authors.affiliation: Division of Inflammation Research, Center for Molecular Medicine.
authors.forename: Motoi
authors.initials: M
authors.lastname: Kobayashi
authors.affiliation: Division of Inflammation Research, Center for Molecular Medicine.
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Mizushina
authors.affiliation: Division of Inflammation Research, Center for Molecular Medicine.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Kasahara
authors.affiliation: Department of Molecular Oncology, Shinshu University Graduate School of Medicine, Nagano; Japan.
authors.forename: Shun'ichiro
authors.initials: S
authors.lastname: Taniguchi
authors.affiliation: Department of Nephrology, Jichi Medical University, Tochigi.
authors.forename: Shigeaki
authors.initials: S
authors.lastname: Muto
authors.affiliation: Department of Nephrology, Jichi Medical University, Tochigi.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Nagata
authors.affiliation: Division of Inflammation Research, Center for Molecular Medicine.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Takahashi
mesh_terms: D058186:Acute Kidney Injury / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D017209:Apoptosis; D015415:Biomarkers; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D015870:Gene Expression; D058847:Inflammasomes / Q000378:metabolism*; D018836:Inflammation Mediators / Q000378:metabolism; D007684:Kidney Tubules / Q000378:metabolism; D007962:Leukocytes / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D012206:Rhabdomyolysis / Q000150:complications*
chemical_list: D015415:Biomarkers; D002352:Carrier Proteins; D016207:Cytokines; D058847:Inflammasomes; D018836:Inflammation Mediators; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse