Calcineurin B1 subunit in human peripheral blood mononuclear cells and its role in idiopathic membranous nephropathy

Calcineurin B1 subunit in human peripheral blood mononuclear cells and its role in idiopathic membranous nephropathy
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人外周血单个核细胞钙调神经磷酸酶B1亚基及其在特发性膜性肾病中的作用

DOI:
10.1097/md.0000000000015231
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发表时间:
2019-04
期刊:
Medicine (Baltimore)
影响因子:
--
通讯作者:
Lin shanyan
Lin shanyan
中科院分区:
其他
文献类型:
--
作者:
Zhu Ying;Zhang min;Wang fan;Sun jing;Lu ji;a;Chen ruiying;Xie qionghong;Xue jun;Hao chuanming;Lin shanyan

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摘要特发性膜性肾病(IMN)发病机制中的免疫反应尚未完全清楚。钙调神经磷酸酶是T细胞活化的关键信号酶,可能与IMN有关。本研究旨在探讨钙调神经磷酸酶B1亚基(CnB 1)在IMN中的作用及其可能机制。共招募了59名经活检证实的IMN患者和28名健康对照。Western blotting检测人外周血单个核细胞(PBMC)中CnB 1的表达。分别用小干扰RNA(siRNA)转染和慢病毒转导方法实现CnB 1在Jurkat T细胞系中的敲低和过表达。结果发现IMN患者PBMC中CnB 1的表达显著增加(P = 0.002),但与IMN的严重程度和预后无关。  Jurkat细胞中CnB 1的敲低抑制了T细胞活化所需的活化T细胞核因子(NFAT)调节的基因表达。提示CnB 1在IMN的发生中可能起重要作用。其作用机制可能与CnB 1对钙调神经磷酸酶-NFAT信号通路介导的T细胞活化的影响有关。
Abstract The immune responses involved in the pathogenesis of idiopathic membranous nephropathy (IMN) have not been fully understood. Calcineurin, a key signaling enzyme in T-cell activation, may be implicated in IMN. The present study aimed to investigate the role of calcineurin B1 subunit (CnB1) in IMN and the potential mechanism. A total of 59 biopsy-proven IMN patients and 28 healthy controls were recruited. The CnB1 expression in human peripheral blood mononuclear cells (PBMCs) was assessed by Western blotting. Knockdown and overexpression of CnB1 in Jurkat T cell line were achieved by small interference RNA (siRNA) transfection and lentiviral transduction, respectively. It was found that PBMCs CnB1 expression was significantly increased in IMN patients (P = .002), but unrelated to the severity and prognosis of IMN. Knockdown of CnB1 in Jurkat cells inhibited the nuclear factor of activated T cells (NFAT)-regulated gene expression required for T-cell activation. Our study suggested the potential role of CnB1 in the occurrence of IMN. The mechanism maybe involved the effect of CnB1 on the T-cell activation mediated by calcineurin-NFAT signaling.
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