类风湿关节炎滑膜成纤维细胞中组蛋白赖氨酸甲基转移酶和去甲基化酶的基因表达谱改变。

Altered gene expression profiles of histone lysine methyltransferases and demethylases in rheumatoid arthritis synovial fibroblasts.

机构信息

Department of Rheumatology and Applied Immunology, Faculty of Medicine, and Project Research Division, Research Center for Genomic Medicine, Saitama Medical University, Saitama, Japan.

Department of Rheumatology and Applied Immunology, Faculty of Medicine, Saitama Medical University, Saitama, Japan.

出版信息

Clin Exp Rheumatol. 2018 Mar-Apr;36(2):314-316. Epub 2018 Jan 31.

PMID:29465369

Abstract

OBJECTIVES

Aberrant histone lysine methylation (HKM) has been reported in rheumatoid arthritis (RA) synovial fibroblasts (SFs). As histone lysine methyltransferases (HKMTs) and demethylases (HKDMs) regulate HKM, these enzymes are believed to be dysregulated in RASFs. The aim of this study is to clarify whether gene expressions of HKMTs and HKDMs are altered in RASFs.

METHODS

SFs were isolated from synovial tissues obtained from RA or osteoarthritis (OA) patients during total knee joint replacement. The mRNA levels of 34 HKMTs and 22 HKDMs were examined after stimulation with tumour necrosis factor α (TNF-α) in RASFs and OASFs.

RESULTS

The gene expression of the 12 HKMTs, including MLL1, MLL3, SUV39H1, SUV39H2, PRDM2, EZH2, SETD2, NSD2, NSD3, SMYD4, DOT1, and PR-set7, that catalyse the methylation of H3K4, H3K9, H3K27, H3K36, H3K79, or H4K20 was higher after TNFα stimulation in RASFs vs. OASFs. The gene expression of the 4 HKDMs, including FBXL10, NO66, JMJD2D, and FBXL11, that catalyse the methylation of H3K4, H3K9, or H3K36 was higher after TNFα stimulation in RASFs vs. OASFs.

CONCLUSIONS

The study findings suggest that the HKM-modifying enzymes are involved in the alteration of HKM, which results in changes in the gene expression of RASFs.

摘要

目的

类风湿关节炎（RA）滑膜成纤维细胞（SF）中存在异常组蛋白赖氨酸甲基化（HKM）。由于组蛋白赖氨酸甲基转移酶（HKMTs）和去甲基化酶（HKDMs）调节 HKM，因此认为这些酶在 RA SFs 中失调。本研究旨在阐明 RA SFs 中 HKMTs 和 HKDMs 的基因表达是否改变。

方法

在全膝关节置换术期间，从 RA 或骨关节炎（OA）患者的滑膜组织中分离 SFs。在 RA SFs 和 OA SFs 中用肿瘤坏死因子 α（TNF-α）刺激后，检查 34 种 HKMTs 和 22 种 HKDMs 的 mRNA 水平。

结果

在 RA SFs 中，12 种 HKMTs（包括 MLL1、MLL3、SUV39H1、SUV39H2、PRDM2、EZH2、SETD2、NSD2、NSD3、SMYD4、DOT1 和 PR-set7）的基因表达，这些酶催化 H3K4、H3K9、H3K27、H3K36、H3K79 或 H4K20 的甲基化，在 TNFα刺激后高于 OA SFs。在 RA SFs 中，4 种 HKDMs（包括 FBXL10、NO66、JMJD2D 和 FBXL11）的基因表达，这些酶催化 H3K4、H3K9 或 H3K36 的甲基化，在 TNFα刺激后高于 OA SFs。