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目的:分析赖氨酸特异性去甲基化酶6B（KDM6B）在乙型肝炎相关性肾炎（HBV-GN）患者肾组织及乙型肝炎病毒X基因（HBx）转染的人足细胞中的表达，及其在HBx介导的足细胞-巨噬细胞转分化（PMT）中的作用。方法:选取2013至2018年在上海交通大学附属第一人民医院经肾穿刺活检病理诊断为HBV-GN的48例患者肾活检标本，以30例原发性肾小球肾炎（PGN）肾活检标本及15例肾肿瘤患者癌旁正常肾组织作为对照。利用免疫荧光及免疫组化法观察HBV-GN患者肾组织KDM6B及巨噬细胞标志物F4/80的表达。分析肾组织KDM6B表达水平与HBV-GN患者临床特征的关系。Western印迹法检测足细胞中KDM6B、F4/80、主要组织相容性复合体Ⅱ（MHC-Ⅱ）以及共刺激分子CD40的表达；ELISA法测定细胞上清中γ干扰素（IFN-γ）、白细胞介素（IL）-6的含量；同时利用KDM6B小干扰RNA（siRNA）沉默HBx质粒转染的人足细胞中KDM6B基因表达后，Western印迹法检测细胞中KDM6B、F4/80及组蛋白H3第27位赖氨酸三甲基化（H3K27me3）的表达变化。结果:与正常对照组相比，HBV-GN患者肾组织KDM6B表达增加（0.022±0.004比0.006±0.002，n P=0.006）。HBV-GN不同病理类型组间KDM6B阳性率差异无统计学意义（n P=0.139）。此外，在HBV-GN患者足细胞中可观察到KDM6B和F4/80的共表达。估算肾小球滤过率（eGFR）<60 ml·minn -1·（1.73 mn 2）n -1或尿蛋白≥3.5 g/d的患者肾组织KDM6B表达分别高于eGFR≥60 ml·minn -1·（1.73 mn 2）n -1或尿蛋白<3.5 g/d的患者（均n P<0.05）。HBx转染人足细胞后KDM6B、F4/80、MHC-Ⅱ以及CD40表达均上调（均n P<0.05），上清IFN-γ和IL-6含量均增加（均n P<0.05）；将KDM6B基因沉默后，HBx所诱导的足细胞F4/80表达下调，H3K27me3表达则上调（均n P<0.05）。n 结论:HBx可通过诱导足细胞KDM6B表达启动PMT，可能参与HBV-GN局部组织免疫微环境紊乱的发生。“,”Objective:To explore the expression of lysine (k)-specific demethylase 6B (KDM6B) in the renal tissues of hepatitis B virus-associated glomerulonephritis (HBV-GN) patients and human podocytes transfected with hepatitis B virus X (HBx) gene, and its role in HBx-mediated podocyte-macrophage transdifferentiation (PMT).Methods:Forty-eight patients diagnosed as HBV-GN by renal biopsy from 2013 to 2018 at the Shanghai Jiaotong University Affiliated First People′s Hospital were included in this study. Thirty patients with primary glomerulonephritis (PGN) and fifteen patients with renal tumor were chosen as control group. The expression of KDM6B and macrophage marker F4/80 in renal tissues of HBV-GN patients was observed by immunofluorescence and immunohistochemistry. The association between kidney KDM6B levels and clinical features of HBV-GN patients was analyzed. The expression of KDM6B, F4/80, major histocompatibility complex (MHC)-Ⅱ and CD40 in the podocytes was detected by Western blotting. The contents of interferon-γ (IFN-γ) and interleukin-6 (IL-6) in the supernatant were determined by enzyme-linked immunosorbent assay (ELISA). The small interfering RNA of KDM6B (KDM6B siRNA) was used to silence the expression of KDM6B and the protein levels of KDM6B, F4/80 and tri-methylation of lysine 27 of histone H3 (H3K27me3) induced by HBx gene transfection were detected by Western blotting.Results:Renal KDM6B expression was significantly increased in HBV-GN patients compared to normal control (0.022±0.004 vs 0.006±0.002, n P=0.006). There was no significant difference in the positive rate of KDM6B among different pathological types of HBV-GN (n P=0.139). Moreover, co-expression of KDM6B and F4/80 could be observed in the podocytes of HBV-GN patients. Patients with estimated glomerular filtration (eGFR)<60 ml·minn -1·(1.73 mn 2)n -1or proteinuria ≥ 3.5 g/day had a significantly higher renal KDM6B expression compared to control groups (all n P<0.05). In addition, the expression of KDM6B, F4/80, MHC-II and CD40 was significantly up-regulated in the podocytes transfected with HBx gene (alln P<0.05). The content of IFN-γ and IL-6 in the supernatant was significantly increased (alln P<0.05). After gene silencing of KDM6B, the expression of F4/80 induced by HBx in the podocytes was significantly down-regulated, while the level of H3K27me3 was significantly increased (bothn P<0.05).n Conclusions:HBx could induce KDM6B expression in podocytes and initiate PMT, thereby involving in the dysfunction of immune microenviroment in the renal tissues of HBV-GN.