Reactive oxygen species promote tubular injury in diabetic nephropathy: The role of the mitochondrial ros-txnip-nlrp3 biological axis.
Reactive oxygen species promote tubular injury in diabetic nephropathy: The role of the mitochondrial ros-txnip-nlrp3 biological axis.
复制标题
活性氧促进糖尿病肾病肾小管损伤：线粒体 ros-txnip-nlrp3 生物轴的作用
DOI：
10.1016/j.redox.2018.02.013
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发表时间：
2018-06
期刊：
影响因子：
11.4
通讯作者：
Sun L
中科院分区：
文献类型：
--
作者：
Han Y;Xu X;Tang C;Gao P;Chen X;Xiong X;Yang M;Yang S;Zhu X;Yuan S;Liu F;Xiao L;Kanwar YS;Sun L
线粒体ROS(MtROS)过度产生后通过硫氧还蛋白(Trx)/硫氧还蛋白相互作用蛋白(TXNIP)激活NLRP3/IL-1β在炎症反应中起关键作用。然而，这一过程在糖尿病肾病患者肾小管损伤中的作用尚不清楚。在这里，我们证明了mtROS的过度生产伴随着TRX表达的减少和TXNIP的上调。此外，我们还发现糖尿病肾病患者和db/db小鼠肾脏mtROS的过度产生也与NLRP3/IL-1β和转化生长因子-β的表达增加有关。我们通过给db/db小鼠腹腔注射MitoQ来逆转这些变化，MitoQ是一种针对mtROS的抗氧化剂。在高糖(HG)条件下和MitoQ处理的人肾小管HK-2细胞中也观察到了类似的结果。用MitoQ处理HK-2细胞，可抑制TRX与TXNIP的解离，进而阻断TXNIP与NLRP3的相互作用，从而抑制NLRP3炎性小体的激活和IL-1β的成熟。在体外，TXNIP siRNA可增强MitoQ的作用，而尿酸单钠(MSU)和Trx siRNA可阻断MitoQ的作用。这些结果提示，线粒体ROS-TXNIP/NLRP3/IL-1β轴的激活与肾小管氧化损伤有关，MitoQ可通过抑制mtROS的过度产生而减轻这种损伤。在糖尿病肾病中，活性氧物种促进肾脏损害。线粒体ROS-TXNIP-NLRP3生物轴参与了糖尿病肾病肾小管损伤。MitoQ抑制线粒体ROS可减轻肾小管损伤。
NLRP3/IL-1β activation via thioredoxin (TRX)/thioredoxin-interacting protein (TXNIP) following mitochondria ROS (mtROS) overproduction plays a key role in inflammation. However, the involvement of this process in tubular damage in the kidneys of patients with diabetic nephropathy (DN) is unclear. Here, we demonstrated that mtROS overproduction is accompanied by decreases in TRX expression and TXNIP up-regulation. In addition, we discovered that mtROS overproduction is also associated with increases in NLRP3/IL-1β and TGF-β expression in the kidneys of patients with DN and db/db mice. We reversed these changes in db/db mice by administering a peritoneal injection of MitoQ, an antioxidant targeting mtROS. Similar results were observed in human tubular HK-2 cells subjected to high-glucose (HG) conditions and treated with MitoQ. Treating HK-2 cells with MitoQ suppressed the dissociation of TRX from TXNIP and subsequently blocked the interaction between TXNIP and NLRP3, leading to the inhibition of NLRP3 inflammasome activation and IL-1β maturation. The effects of MitoQ were enhanced by pretreatment with TXNIP siRNA and abolished by pretreatment with monosodium urate (MSU) and TRX siRNA in vitro. These results suggest that mitochondrial ROS-TXNIP/NLRP3/IL-1β axis activation is responsible for tubular oxidative injury, which can be ameliorated by MitoQ via the inhibition of mtROS overproduction. Reactive oxygen species promotes renal damage in diabetic nephropathy. Mitochondrial ROS- TXNIP-NLRP3 biological axis involved in tubular injury of DN. Inhibition of mitochondrial ROS by MitoQ ameliorated the renal tubular injury.
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NADPH 氧化酶诱导的 NALP3 炎症小体激活是由硫氧还蛋白相互作用蛋白驱动的，硫氧还蛋白相互作用蛋白导致高血糖时足细胞损伤。
影响因子：
4.3
作者：
Gao P;He FF;Tang H;Lei CT;Chen S;Meng XF;Su H;Zhang C
通讯作者：
Zhang C
DOI：
10.1523/jneurosci.0552-11.2011
发表时间：
2011-11-02
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
McManus MJ;Murphy MP;Franklin JL
通讯作者：
Franklin JL
影响因子：
4.3
作者：
Fang, Shaohong;Jin, Yuhong;Zhou, Hongbo
通讯作者：
Zhou, Hongbo
DOI：
10.4997/jrcpe.2013.413
发表时间：
2013-01-01
影响因子：
1.4
作者：
Chan, G.;Tang, S. C-W
通讯作者：
Tang, S. C-W
Ilexgenin A 通过 AMPK 依赖性方式抑制 TXNIP/NLRP3 炎症小体激活，抑制内质网应激并改善内皮功能障碍
影响因子：
9.3
作者：
Li, Yi;Yang, Jie;Wen, Xiao-Dong
通讯作者：
Wen, Xiao-Dong