CD36-Mediated Lipid Accumulation and Activation of NLRP3 Inflammasome Lead to Podocyte Injury in Obesity-Related Glomerulopathy
CD36-Mediated Lipid Accumulation and Activation of NLRP3 Inflammasome Lead to Podocyte Injury in Obesity-Related Glomerulopathy
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CD36 介导的脂质积累和 NLRP3 炎性体激活导致肥胖相关肾小球病足细胞损伤
DOI：
10.1155/2019/3172647
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发表时间：
2019-04
影响因子：
4.6
通讯作者：
Cheng Hong
中科院分区：
文献类型：
--
作者：
Zhao Jing;Rui Hong liang;Yang Min;Sun Li jun;Dong Hong rui;Cheng Hong
足细胞损伤在肥胖相关性肾小球病（ORG）的发病机制中起重要作用。近年来，研究发现脂质积聚和炎症反应与足细胞损伤有关。在动物实验中，ORG小鼠出现蛋白尿、足细胞损伤和高脂血症，并伴有脂质代谢紊乱、肾脏异位脂质沉积、NOD样受体蛋白3（NLRP 3）炎性小体激活和IL-1β分泌。肾组织中脂肪分化相关蛋白（ADRP）、CD 36、固醇调节元件结合蛋白1（SREBP-1）和过氧化物酶体增殖物激活受体α（PPARα）的表达增加。在体外细胞实验中，与ORG小鼠相似，用瘦素刺激培养的足细胞后，足细胞损伤加重，脂滴形成，ADRP和CD 36表达增加，NLRP 3炎性小体激活，IL-1β释放。另外，用抑制剂硫代琥珀酰亚胺油酸酯（SSO）或CD 36 siRNA阻断CD 36后，NLRP 3炎性体的激活和IL-1β的释放下调，足细胞损伤减轻。用MCC 950阻断NLRP 3后，足细胞损伤减轻，IL-1β释放减少，但CD 36、ADRP和细胞内脂滴的表达无明显变化。综上所述，我们的研究表明，CD 36介导的脂质积聚和NLRP 3炎性体的激活可能是ORG足细胞损伤的潜在发病机制之一。
Podocyte injury critically contributes to the pathogenesis of obesity-related glomerulopathy (ORG). Recently, lipid accumulation and inflammatory responses have been found to be involved in podocyte injury. This study is to explore their role and relationship in podocyte injury of ORG. In animal experiments, the ORG mice developed proteinuria, podocyte injury, and hypertriglyceridemia, accompanied with deregulated lipid metabolism, renal ectopic lipid deposition, activation of NOD-like receptor protein 3 (NLRP3) inflammasome, and secretion of IL-1β of the kidney. The expression of adipose differentiation-related protein (ADRP), CD36, sterol regulatory element-binding protein 1 (SREBP-1), and peroxisome proliferator-activated receptor α (PPARα) in renal tissue were increased. In in vitro cell experiments, after cultured podocytes were stimulated with leptin, similar to ORG mice, we found aggravated podocyte injury, formatted lipid droplet, increased expression of ADRP and CD36, activated NLRP3 inflammasome, and released IL-1β. In addition, after blocking CD36 with inhibitor sulfo-N-succinimidyl oleate (SSO) or CD36 siRNA, activation of NLRP3 inflammasome and release of IL-1β are downregulated, and podocyte injury was alleviated. However, after blocking NLRP3 with MCC950, although podocyte injury was alleviated and release of IL-1β was decreased, there was no change in the expression of CD36, ADRP, and intracellular lipid droplets. Taken together, our study suggests that CD36-mediated lipid accumulation and activation of NLRP3 inflammasome may be one of the potential pathogeneses of ORG podocyte injury.
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DOI：
10.4049/jimmunol.1601563
发表时间：
2017-03-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Rhoads JP;Lukens JR;Wilhelm AJ;Moore JL;Mendez-Fernandez Y;Kanneganti TD;Major AS
通讯作者：
Major AS
影响因子：
9
作者：
Xu S;Nam SM;Kim JH;Das R;Choi SK;Nguyen TT;Quan X;Choi SJ;Chung CH;Lee EY;Lee IK;Wiederkehr A;Wollheim CB;Cha SK;Park KS
通讯作者：
Park KS
嘌呤能 2X7 受体通过激活核苷酸结合和寡聚结构域样受体蛋白 3 炎症小体参与肥胖相关肾小球病的足细胞损伤。
影响因子：
6.1
作者：
Hou XX;Dong HR;Sun LJ;Yang M;Cheng H;Chen YP
通讯作者：
Chen YP
抑制 NLRP3 炎症小体可通过抑制 ox-LDL 摄取和促进胆固醇流出来减弱 THP-1 巨噬细胞泡沫细胞的形成
DOI：
10.1016/j.bbrc.2017.11.025
发表时间：
2018-01-01
影响因子：
3.1
作者：
Chen, Liang;Yao, Qiying;Qu, Peng
通讯作者：
Qu, Peng
影响因子：
16
作者：
Martinon, F;Burns, K;Tschopp, J
通讯作者：
Tschopp, J