The Expression and Significance of NLRP3 Inflammasome in Patients with Primary Glomerular Diseases
The Expression and Significance of NLRP3 Inflammasome in Patients with Primary Glomerular Diseases
复制标题
NLRP3炎症小体在原发性肾小球疾病患者中的表达及意义。
DOI：
10.1159/000368511
复制
发表时间：
2015-01-01
影响因子：
2.8
通讯作者：
Meng, Xian-Fang
中科院分区：
文献类型：
--
作者：
Xiong, Jing;Wang, Yang;Meng, Xian-Fang
背景/目的：原发性肾小球肾炎（PGN）是中国最常见的导致终末期肾病的原因，但其发病机制尚不清楚。本研究旨在验证NLRP3 （Nod-like receptor family pyrin domain containing 3）炎性小体的形成和激活是导致PGN的重要启动机制。方法：采集38例PGN患者的血清和冰冻切片，其中22例取肾组织。采用RT-PCR和免疫荧光法检测NLRP3炎性小体。分析NLRP3与临床病理指标的关系。结果：RT-PCR分析显示，与正常癌周组织相比，PGN患者肾组织中NLRP3和caspase-1基因mRNA水平显著升高。NLRP3 mRNA水平升高与nephrin mRNA水平降低、desmin mRNA水平升高相关，提示NLRP3参与了PGN患者足细胞损伤。免疫荧光分析还显示，PGN患者肾小球中NLRP3和caspase-1蛋白表达升高。但进一步按病理类型进行亚组分析，无明显规律性。此外，NLRP3升高与肾功能恶化和肾小球硬化相关。IL-1 β是NLRP3炎性体激活的产物，与蛋白尿有显著相关性。结论：足细胞中NLRP3炎性小体的形成和激活与pgnn相关肾小球损伤的发展有重要关系。巴塞尔S. Karger股份有限公司版权所有
Background/Aims: Primary glomerulonephritis (PGN) is the most common reason inducing end stage renal disease in China, however, its pathogenesis remains unclear. The present study was designed to test the hypothesis that the formation and activation of NLRP3 (Nod-like receptor family pyrin domain containing 3) inflammasomes is an important initiating mechanism resulting in PGN. Methods: Serum samples and frozen sections were collected from 38 cases with PGN, and renal tissues were obtained from 22 of them. NLRP3 inflammasomes were detected by RT-PCR and immunofluoresence methods. The relationship between NLRP3 and clinical/pathologic indexes was analyzed. Results: RT-PCR analyses demonstrated that the mRNA levels of NLRP3 and caspase-1 genes were elevated significantly in renal tissues of PGN patients compared to those from normal pericarcinoma tissues. Moreover, the increased level of NLRP3 mRNA was correlative with a decrease in nephrin mRNA level and an increase in desmin mRNA level, which indicates that NLRP3 participates in podocyte injury in PGN patients. Immunofluorescence analysis also showed the protein expressions of NLRP3 and caspase-1 were increased in the glomeruli of PGN patients. Neverthless, there was no obvious regularity was presented in further subgroup analysis according to pathological types. In addition, increased NLRP3 was associated with the deterioration of renal function and glomerulosclerosis. IL-1 beta, a product of NLRP3 inflammasome activation, had a significant correlation with proteinuria. Conclusions: The formation and activation of NLRP3 inflammasomes in podocytes has been importantly implicated in the development of PGN-associated glomerular injury. Copyright (C) 2015 S. Karger AG, Basel