First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
Arthritis Rheumatol. 2017 Aug;69(8):1636-1646. doi: 10.1002/art.40155. Epub 2017 Jun 26.
Development of proteinuria in lupus nephritis (LN) is associated with podocyte dysfunction. The NLRP3 inflammasome has been implicated in the pathogenesis of LN. The purpose of this study was to investigate whether NLRP3 inflammasome activation is involved in the development of podocyte injury in LN.
A fluorescence-labeled caspase 1 inhibitor probe was used to detect the activation of NLRP3 inflammasomes in podocytes derived from lupus-prone NZM2328 mice and from renal biopsy tissues obtained from patients with LN. MCC950, a selective inhibitor of NLRP3, was used to treat NZM2328 mice. Proteinuria, podocyte ultrastructure, and renal pathology were evaluated. In vitro, sera from diseased NZM2328 mice were used to stimulate a podocyte cell line, and the cells were analyzed by flow cytometry.
NLRP3 inflammasomes were activated in podocytes from lupus-prone mice and from patients with LN. Inhibition of NLRP3 with MCC950 ameliorated proteinuria, renal histologic lesions, and podocyte foot process effacement in lupus-prone mice. In vitro, sera from diseased NZM2328 mice activated NLRP3 inflammasomes in the podocyte cell line through the production of reactive oxygen species.
NLRP3 inflammasomes were activated in podocytes from lupus-prone mice and from LN patients. Activation of NLRP3 is involved in the pathogenesis of podocyte injuries and the development of proteinuria in LN.
狼疮肾炎（LN）患者的蛋白尿发展与足细胞功能障碍有关。NLRP3 炎性小体与 LN 的发病机制有关。本研究旨在探讨 NLRP3 炎性小体的激活是否参与 LN 中足细胞损伤的发生。
使用荧光标记的半胱天冬酶 1 抑制剂探针检测狼疮易感 NZM2328 小鼠来源的足细胞和 LN 患者肾活检组织中 NLRP3 炎性小体的激活。使用 NLRP3 的选择性抑制剂 MCC950 治疗 NZM2328 小鼠。评估蛋白尿、足细胞超微结构和肾脏病理。在体外，使用来自患病 NZM2328 小鼠的血清刺激足细胞系，并通过流式细胞术分析细胞。
NLRP3 炎性小体在狼疮易感小鼠和 LN 患者的足细胞中被激活。用 MCC950 抑制 NLRP3 可改善狼疮易感小鼠的蛋白尿、肾脏组织学病变和足细胞足突融合。在体外，来自患病 NZM2328 小鼠的血清通过产生活性氧来激活足细胞系中的 NLRP3 炎性小体。
NLRP3 炎性小体在狼疮易感小鼠和 LN 患者的足细胞中被激活。NLRP3 的激活参与了 LN 中足细胞损伤和蛋白尿发展的发病机制。
