NLRP3 Deficiency Attenuates Renal Fibrosis and Ameliorates Mitochondrial Dysfunction in a Mouse Unilateral Ureteral Obstruction Model of Chronic Kidney Disease.
NLRP3 Deficiency Attenuates Renal Fibrosis and Ameliorates Mitochondrial Dysfunction in a Mouse Unilateral Ureteral Obstruction Model of Chronic Kidney Disease.
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DOI：
10.1155/2017/8316560
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发表时间：
2017
影响因子：
4.6
通讯作者：
Ding W
中科院分区：
文献类型：
--
作者：
Guo H;Bi X;Zhou P;Zhu S;Ding W
背景和目的。含有PYD-3 （NLRP3）炎症小体的核苷酸结合域和富含亮氨酸的重复序列与慢性肾脏疾病（CKD）的发病机制有关；然而，其在肾小球损伤和小管间质纤维化中的确切作用仍不清楚。本研究旨在确定NLRP3在CKD小鼠单侧输尿管梗阻（UUO）模型中调节肾损伤和纤维化的功能，以及线粒体功能障碍的潜在参与。方法。采用野生型（WT）和NLRP3−/−小鼠，我们评估了肾脏结构、组织损伤和线粒体超微结构，以及参与纤维化、凋亡、炎症和线粒体功能障碍进展的一些重要分子的表达。结果。UUO在NLRP3 - / -小鼠中显著减轻了WT小鼠严重的肾小球损伤和小管间质纤维化，这可以通过阻断细胞外基质沉积、减少细胞凋亡和表型改变来证明。此外，NLRP3缺失逆转了uuo诱导的线粒体形态和功能损伤。结论。NLRP3缺失可改善CKD小鼠UUO模型的线粒体功能障碍并减轻肾纤维化。
Background and Aims. The nucleotide-binding domain and leucine-rich repeat containing PYD-3 (NLRP3) inflammasome has been implicated in the pathogenesis of chronic kidney disease (CKD); however, its exact role in glomerular injury and tubulointerstitial fibrosis is still undefined. The present study was performed to identify the function of NLRP3 in modulating renal injury and fibrosis and the potential involvement of mitochondrial dysfunction in the murine unilateral ureteral obstruction (UUO) model of CKD. Methods. Employing wild-type (WT) and NLRP3−/− mice with or without UUO, we evaluated renal structure, tissue injury, and mitochondrial ultrastructure, as well as expression of some vital molecules involved in the progression of fibrosis, apoptosis, inflammation, and mitochondrial dysfunction. Results. The severe glomerular injury and tubulointerstitial fibrosis induced in WT mice by UUO was markedly attenuated in NLRP3−/− mice as evidenced by blockade of extracellular matrix deposition, decreased cell apoptosis, and phenotypic alterations. Moreover, NLRP3 deletion reversed UUO-induced impairment of mitochondrial morphology and function. Conclusions. NLRP3 deletion ameliorates mitochondrial dysfunction and alleviates renal fibrosis in a murine UUO model of CKD.