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DNA低甲基化在系统性红斑狼疮诱导中的可能作用:与人类内源性逆转录病毒转录的关系

Possible role of DNA hypomethylation in the induction of SLE: relationship to the transcription of human endogenous retroviruses.

作者信息

Ogasawara H, Okada M, Kaneko H, Hishikawa T, Sekigawa I, Hashimoto H

机构信息

Department of Internal Medicine and Rheumatology, Juntendo University School of Medicine, Tokyo, Japan.

出版信息

Clin Exp Rheumatol. 2003 Nov-Dec;21(6):733-8.

Abstract

OBJECTIVE

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).

METHODS

The reverse transcriptase-polymerase chain reaction (RT-PCR) and real-time quantitative-PCR (RQ-PCR) were used.

RESULTS

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.

CONCLUSION

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.

摘要

目的

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。

方法

采用逆转录聚合酶链反应(RT-PCR)和实时定量PCR(RQ-PCR)。

结果

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。

结论

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。

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