Role of NLRP3 Inflammasomes for Rhabdomyolysis-induced Acute Kidney Injury.
Role of NLRP3 Inflammasomes for Rhabdomyolysis-induced Acute Kidney Injury.
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DOI：
10.1038/srep10901
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发表时间：
2015-06-05
影响因子：
4.6
通讯作者：
Takahashi M
中科院分区：
文献类型：
--
作者：
Komada T;Usui F;Kawashima A;Kimura H;Karasawa T;Inoue Y;Kobayashi M;Mizushina Y;Kasahara T;Taniguchi S;Muto S;Nagata D;Takahashi M
横纹肌溶解是社区获得性急性肾损伤的主要原因之一。虽然炎症参与了横纹肌溶解诱导AKI(RIAKI)的发病机制，但在RIAKI过程中引发炎症的机制尚不清楚。最近的证据表明，由组织损伤引发的无菌炎症可以通过称为炎性小体的多蛋白复合体来介导。因此，我们利用甘油诱导的小鼠横纹肌溶解模型研究了NLRP3炎性小体在RIAKI发病机制中的作用。炎症体相关分子在RIAKI肾脏中表达上调。在RIAKI早期，肾小管损伤和功能障碍先于白细胞进入肾脏，与野生型小鼠相比，NLRP3、Asc、Caspase-1和IL-1β缺陷小鼠的肾小管损伤和功能障碍明显减轻。野生型和NLRP3基因缺陷小鼠的白细胞浸润无明显差异。此外，NLRP3缺乏可显著抑制肾损伤标志物和炎性细胞因子的表达以及肾小管细胞的凋亡。这些结果表明，NLRP3炎性小体参与了RIAKI早期的炎症、细胞凋亡和组织损伤，并为RIAKI的发病机制提供了新的见解。
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.
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影响因子：
29.7
作者：
Davis BK;Wen H;Ting JP
通讯作者：
Ting JP
DOI：
10.1053/j.ajkd.2009.12.034
发表时间：
2010-07
期刊：
American journal of kidney diseases : the official journal of the National Kidney Foundation
影响因子：
--
作者：
Coca SG
通讯作者：
Coca SG
影响因子：
13.6
作者：
Belliere, Julie;Casemayou, Audrey;Bascands, Jean-Loup
通讯作者：
Bascands, Jean-Loup
DOI：
10.1124/jpet.113.205732
发表时间：
2013-09-01
影响因子：
3.5
作者：
Kim, Hyun-Jung;Lee, Dong Won;Edelstein, Charles L.
通讯作者：
Edelstein, Charles L.
DOI：
10.1083/jcb.200903124
发表时间：
2009-10-05
期刊：
The Journal of cell biology
影响因子：
--
作者：
Lamkanfi M;Mueller JL;Vitari AC;Misaghi S;Fedorova A;Deshayes K;Lee WP;Hoffman HM;Dixit VM
通讯作者：
Dixit VM