上海交通大学学报（医学版）

上海交通大学学报(医学版) ›› 2020, Vol. 40 ›› Issue (08): 1063-1068.doi: 10.3969/j.issn.1674-8115.2020.08.010

• 论著·基础研究 • 上一篇    下一篇

组蛋白乙酰化在IgA肾病发病中的作用

戴 芹1，王伟铭2   

  1. 1. 复旦大学附属中山医院徐汇医院肾内科，上海 200031；2.上海交通大学医学院附属瑞金医院肾内科，上海 200025
  • 出版日期:2020-08-28 发布日期:2020-08-28
  • 通讯作者: 王伟铭，电子信箱：wweiming@medmail.com.cn。
  • 作者简介:戴 芹（1978—），女，副主任医师，博士；电子信箱：dai11qin@sina.com。
  • 基金资助:
    上海市卫健委课题（201640045）；上海市高级中西医结合人才培养项目 [ZY(2018-2020)-RCPY-2020];上海市徐汇区卫生健康系统人才培养项目（xhxtrc2019-2021）。

Role of histone acetylation in the pathogenesis of IgA nephropathy

DAI Qin1, WANG Wei-ming2   

  1. 1. Department of Nephrology, Xuhui hospital, Zhongshan Hospital, Fudan University ,Shanghai 200031,China; 2. Department of Nephrology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
  • Online:2020-08-28 Published:2020-08-28
  • Supported by:
    Project of Shanghai Municipal Health Commission (201640045); Shanghai Senior Integrated Traditional Chinese and Western Medicine Talents Training Project [ZY(2018-2020)-RCPY-2020]; Personnel Training Project of Health System in Xuhui District of Shanghai (xhxtrc2019-2021).

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摘要： 目的·研究组蛋白乙酰化修饰在IgA肾病（IgA nephropathy，IgAN）发病机制中的作用，从表观遗传学角度探讨IgAN的发病机制。方法·纳入原发性IgAN患者（IgAN组）30例，对照组19例(血液样本对照组16例，正常肾组织样本对照组3例)。收集外周静脉血提取单个核细胞（peripheral blood mononuclear cell, PBMC）用于检测。ELISA法检测IgAN组及对照组PBMC中组蛋白H3和H4乙酰化水平。Real-time PCR法检测P300、CREBBP、HDAC1-3、HDAC7、HDAC8、C1GALT1和ST6GALNAC2 mRNA表达。染色质免疫共沉淀法检测C1GALT1和ST6GALNAC2基因启动子区组蛋白H3和H4乙酰化水平。免疫荧光法检测肾组织中HDAC1和H3Ac的蛋白表达量。采用t检验进行统计分析。结果·与对照组比较，IgAN组组蛋白H3和H4乙酰化水平均显著升高（P=0.035，P=0.012）；IgAN组P300、CREBBP、HDAC1、HDAC8和ST6GALNAC2 mRNA的表达显著升高（P=0.002，P=0.001，P=0.001，P=0.045，P=0.012），HDAC2和C1GALT1的mRNA表达量显著下降（P=0.035，P=0.008）；IgAN组 C1GALT1基因启动子区域组蛋白H3和H4乙酰化程度显著降低（P=0.043，P=0.005）；ST6GALNAC2基因启动子区域组蛋白H3和H4乙酰化程度均显著升高（P=0.038，P=0.021）。IgAN患者肾小球及肾小管中HDAC1表达明显增多，而H3Ac蛋白表达显著减少。结论·IgAN患者存在组蛋白乙酰化修饰异常，组蛋白乙酰化修饰可能通过调控糖基化酶基因表达，从而参与IgAN的发病。

关键词: IgA肾病, 糖基化酶, 组蛋白乙酰化, 表观遗传学

Abstract:

Objective · To study the role of abnormal histone acetylation modification in the pathogenesis of IgA nephropathy (IgAN), and explore the pathogenesis of IgAN from the perspective of epigenetics. Methods · 30 patients with primary IgAN and 19 healthy controls were included. Of the 19 controls, 16 cases were used to collect blood samples and 3 cases were used to collect normal renal tissues. Peripheral venous blood was collected to extract mononuclear cells (PBMC) for detection. The levels of histone H3 and H4 acetylation in PBMC of IgAN group and healthy control group were detected by ELISA. Real-time PCR was used to detect the mRNA expressions of P300、CREBBP、HDAC1-3、HDAC7、HDAC8、C1GALT1 and ST6GALNAC2. The acetylation levels of histone H3 and H4 in promoter regions of C1GALT1 and ST6GALNAC2 were detected by chromatin immune-precipitation (CHIP). The protein expression of HDAC1 and H3Ac was detected by immunofluorescence. T-test was used for statistical analysis. Results · Compared with the healthy control group, the acetylation levels of H3 and H4 in IgAN group were significantly higher than those in healthy control group (P=0.035, P=0.012)；the mRNA expressions of P300, CREBBP, HDAC1, HDAC8 and ST6GALNAC2 were significantly increased in IgAN group (P=0.002, P=0.001, P=0.001, P=0.045 P=0.012); the mRNA expressions of HDAC2 and C1GALT1 were decreased significantly (P=0.035, P=0.008)； the acetylation degree of H3 and H4 in C1GALT1 promoter region was significantly decreased (P=0.043, P=0.005), the degree of H3 and H4 acetylation in the promoter region of ST6GALNAC2 gene was increased significantly in IgAN group (P=0.038, P=0.021);immune fluorescent results of renal tissue indicated that the HDAC1 protein expression was increased obviously, and H3Ac protein expression was significantly reduced in the renal tissue of IgAN patiegts. Conclusion · Abnormal acetylation modification exists in IgAN patients. Histone acetylation modification may participate in the pathogenesis of IgAN by regulating the expression of glycosylase gene.

Key words: IgA nephropathy, glycosylase, histone acetylation, epigenetics

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