Ogasawara H, Okada M, Kaneko H, Hishikawa T, Sekigawa I, Hashimoto H
Department of Internal Medicine and Rheumatology, Juntendo University School of Medicine, Tokyo, Japan.
Clin Exp Rheumatol. 2003 Nov-Dec;21(6):733-8.
We investigated the contribution of DNA methyltransferase activity to the transcription of human endogenous retroviruses (HERV), which have been reported to be a plausible causative agent for systemic lupus erythematosus (SLE).
The reverse transcriptase-polymerase chain reaction (RT-PCR) and real-time quantitative-PCR (RQ-PCR) were used.
Our results indicated that treatment with 5-aza-deoxycytidine (5-aza C), a demethylating agent, increased the transcription of messenger RNA (mRNA) for HERV clone 4-1 and decreased mRNA for DNA methyltransferase-1 (DNMT-1; methylation-regulating enzyme) in peripheral blood mononuclear cells (PBMC) from normal individuals. Also, transcription of DNMT-1 mRNA in PBMC from patients with SLE was lower than in cells from normal controls.
DNA hypomethylation seems to play a significant role in the transcription of HERV clone 4-1 and may be related to the pathogenesis of SLE.
我们研究了DNA甲基转移酶活性对人类内源性逆转录病毒(HERV)转录的作用,据报道,HERV可能是系统性红斑狼疮(SLE)的致病因素。
采用逆转录聚合酶链反应(RT-PCR)和实时定量PCR(RQ-PCR)。
我们的结果表明,用去甲基化剂5-氮杂脱氧胞苷(5-aza C)处理可增加正常个体外周血单个核细胞(PBMC)中HERV克隆4-1信使RNA(mRNA)的转录,并降低DNA甲基转移酶-1(DNMT-1;甲基化调节酶)的mRNA水平。此外,SLE患者PBMC中DNMT-1 mRNA的转录低于正常对照细胞。
DNA低甲基化似乎在HERV克隆4-1的转录中起重要作用,可能与SLE的发病机制有关。