NADPH oxidase-induced NALP3 inflammasome activation is driven by thioredoxin-interacting protein which contributes to podocyte injury in hyperglycemia.
NADPH oxidase-induced NALP3 inflammasome activation is driven by thioredoxin-interacting protein which contributes to podocyte injury in hyperglycemia.
复制标题
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。
DOI：
10.1155/2015/504761
复制
发表时间：
2015
影响因子：
4.3
通讯作者：
Zhang C
中科院分区：
文献类型：
--
作者：
Gao P;He FF;Tang H;Lei CT;Chen S;Meng XF;Su H;Zhang C
糖尿病肾病（Diabetic nephropathy， DN）是终末期肾脏疾病的主要病因之一，先前我们证实NALP3炎性体参与了DN的发病机制。在此，我们研究了NALP3炎性体在DN期间足细胞损伤中的激活机制。我们发现，除了NALP3炎性体的激活和硫氧还蛋白相互作用蛋白（TXNIP）的上调外，NADPH氧化酶亚基gp91phox在DN小鼠肾小球中的表达也同时增强。抑制NADPH氧化酶可消除NALP3炎性体激活和IL-1β的产生，最终保护足细胞免受高糖（HG-）诱导的损伤。TXNIP是硫氧还蛋白的抑制剂，是抗氧化防御系统的抑制因子。我们的观察表明，在hg暴露的足细胞中，通过shRNA基因缺失TXNIP可以逆转gp91phox的过表达，减轻足细胞的损伤。总之，我们的研究结果表明，hg诱导的NADPH氧化酶激活是由TXNIP驱动的，TXNIP随后触发足细胞中NALP3炎性体的激活，最终导致足细胞损伤，阻断TXNIP/NADPH氧化酶信号传导可能是治疗DN的一种有希望的方法。
Diabetic nephropathy (DN) is one of the major causes of end-stage renal disease, and previously we demonstrated that NALP3 inflammasome was involved in the pathogenesis of DN. Here we investigated the mechanisms of NALP3 inflammasome activation in podocyte injury during DN. We found that, besides the activation of NALP3 inflammasome and upregulated thioredoxin-interacting protein (TXNIP), the glomerular expression of gp91phox, a subunit of NADPH oxidase, was enhanced in DN mice simultaneously. Inhibiting NADPH oxidase abrogated NALP3 inflammasome activation, and IL-1β production and eventually protected podocytes from high glucose- (HG-) induced injury. TXNIP, an inhibitor of thioredoxin, acts as a suppressor for antioxidant defense system. Our observation indicated that in HG-exposed podocytes genetic deletion of TXNIP by shRNA reversed gp91phox overexpression and alleviated the injury of podocyte. Collectively, our findings proposed that HG-induced NADPH oxidase activation was driven by TXNIP which subsequently triggered NALP3 inflammasome activation in podocytes and ultimately led to podocyte injury, and blocking TXNIP/NADPH oxidase signaling may be a promising treatment for DN.
登录
查看更多内容
影响因子：
4.8
作者：
Gorin, Y;Block, K;Abboud, HE
通讯作者：
Abboud, HE
影响因子：
5.5
作者：
Demento SL;Eisenbarth SC;Foellmer HG;Platt C;Caplan MJ;Mark Saltzman W;Mellman I;Ledizet M;Fikrig E;Flavell RA;Fahmy TM
通讯作者：
Fahmy TM
DOI：
10.1016/0167-4781(94)90242-9
发表时间：
1994-09-13
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA-GENE STRUCTURE AND EXPRESSION
影响因子：
--
作者：
CHEN, KS;DELUCA, HF
通讯作者：
DELUCA, HF
影响因子：
19.6
作者：
Kobayashi, T;Uehara, S;Kotani, H
通讯作者：
Kotani, H
DOI：
10.4049/jimmunol.0900173
发表时间：
2009-07-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Franchi L;Eigenbrod T;Núñez G
通讯作者：
Núñez G