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J Dermatol Sci. 2013 Jan;69(1):61-7. doi: 10.1016/j.jdermsci.2012.10.011. Epub 2012 Oct 24.

MicroRNA-29b contributes to DNA hypomethylation of CD4+ T cells in systemic lupus erythematosus by indirectly targeting DNA methyltransferase 1.

Author information

1
Department of Dermatology, Huashan Hospital, Fudan University, Shanghai 200040, China.

Abstract

BACKGROUND:

The mechanism of DNA hypomethylation in systemic lupus erythematosus (SLE) has not been fully elucidated. Recent studies showed that miR-29b could regulate DNA methylation by targeting the DNA methylation machinery. However, the role of miR-29b in T cell aberrant DNA hypomethylation of SLE still remains unclear.

OBJECTIVE:

In this study, we asked whether miR-29b regulate DNA methylation in lupus CD4+ T cells.

METHODS:

The miR-29b expression was analyzed by quantitative polymerase chain reaction (qPCR). Sp1, DNMT1, CD11a and CD70 mRNA and protein levels were determined by qPCR, Western-blotting and flow cytometry, respectively. The global DNA methylation levels were evaluated by the Methyflash™ DNA Methylation Quantification Kit. CD11a and CD70 promoter methyaltion levels were detected by bisulfate modification and methylation-sensitive high resolution melting analysis.

RESULTS:

In SLE patients, the miR-29b levels were up-regulated as compared to healthy donors and its degree of overexpression was negatively correlated with sp1 and DNMT1 protein levels, respectively. Overexpression of miR-29b resulted in significant reduction of sp1 and DNMT1 expression. Further analysis demonstrated that overexpression of miR-29b in CD4+ T cells from healthy donors led to the DNA hypomethylation and up-regulation of genes encoding CD11a and CD70, and inhibition of miR-29b expression in CD4+ T cells from patients with lupus caused reverse effects.

CONCLUSION:

Our study suggests that miR-29b negatively regulates DNMT1 expression by targeting sp1 in T cells. The overexpression of miR-29b contributes to the reduction of DNMT1 levels and thereby DNA hypomethylation in SLE. This finding provides potential novel strategies for therapeutic interventions.

PMID:
23142053
DOI:
10.1016/j.jdermsci.2012.10.011
[Indexed for MEDLINE]

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