@entity14540 ( @entity14540 ) contributes to the development of polymicrobial septic AKI. However, the mechanisms that activate the @entity14540 pathway and cause @entity8 during @entity295 remain unknown. To determine the role of mitochondrial DNA (mtDNA) in @entity14540 -associated septic AKI, we established a cecal ligation and puncture (CLP) model of @entity295 in wild-type (WT) and @entity14540 -knockout (Tlr9KO) @entity19 . We evaluated systemic circulation and peritoneal cavity dynamics and immune response and tubular mitochondrial dysfunction to determine upstream and downstream effects on the @entity14540 pathway, respectively. CLP increased mtDNA levels in the plasma and peritoneal cavity of WT and Tlr9KO @entity19 in the early phase, but the increase in the peritoneal cavity was significantly higher in Tlr9KO @entity19 than in WT @entity19 . Concomitantly, leukocyte migration to the peritoneal cavity increased, and plasma cytokine production and splenic apoptosis decreased in Tlr9KO @entity19 compared with WT @entity19 . Furthermore, CLP-generated renal mitochondrial oxidative stress and mitochondrial vacuolization in the proximal tubules in the early phase were reversed in Tlr9KO @entity19 . To elucidate the effects of mtDNA on immune response and @entity8 , we intravenously injected @entity19 with @entity2383 ( @entity2383 ), including substantial amounts of mtDNA. @entity2383 caused an immune response similar to that induced by CLP, including upregulated levels of plasma IL-12, splenic apoptosis, and @entity2383 , but this effect was attenuated by Tlr9KO. Moreover, @entity2383 -induced @entity8 was abolished by DNase pretreatment. These findings suggest that mtDNA activates @entity14540 and contributes to cytokine production, splenic apoptosis, and @entity8 during polymicrobial @entity295 .

Role of Mitochondrial DNA in Septic AKI via XXXX .

@entity8 :: ('MESH:D007674', 'Disease') :: ['kidney injury', 'renal mitochondrial injury'] @entity295 :: ('MESH:D018805', 'Disease') :: ['sepsis'] @entity19 :: ('10090', 'Species') :: ['mice'] @entity14540 :: ('81897(Tax:10090)', 'Gene') :: ['TLR9', 'Toll-like receptor 9', 'Tlr9'] @entity2383 :: ('MESH:D028361', 'Disease') :: ['mitochondrial injury', 'mitochondrial debris', 'MTD']
@entity14540 :: (81897(Tax:10090),Gene) :: ['Toll-Like Receptor 9']
