Transcript overexpression of the MBD2 and MBD4 genes in CD4+ T cells from systemic lupus erythematosus patients
Transcript overexpression of the MBD2 and MBD4 genes in CD4+ T cells from systemic lupus erythematosus patients
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DOI：
10.1189/jlb.0107064
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发表时间：
2007-06-01
影响因子：
5.5
通讯作者：
Vilardell-Tarres, MiqLjel
中科院分区：
文献类型：
--
作者：
Balada, Eva;Ordi-Ros, Josep;Vilardell-Tarres, MiqLjel
系统性红斑狼疮（SLE）患者CD 4 + T细胞DNA低甲基化，可能与SLE的发病机制有关。我们研究了整体DNA甲基化和两个甲基CpG结合结构域（MBD）蛋白表达之间的关系。用ELISA法检测了29例SLE患者和30例健康对照者的CD_4 ~+ T细胞DNA脱氧甲基胞嘧啶（d（m）C）含量。通过实时RT-PCR定量两种甲基CpG结合蛋白（MBD 2和MBD 4）的转录水平。相关性研究还进行了几个实验室参数，以及与患者的临床表现。SLE患者CD 4 + T细胞DNA d（m）C含量显著低于对照组（0.802 +/- 0.134 vs. 0.901 +/- 0.133; P=0.007）。MBD 2和MBD 4 mRNA水平在患者组中显著较高：分别为0.975 +/- 0683和0.604 +/- 0.614（P=0.004），0.359 +/- 0.330和0.092 +/- 0.169（P < 0.0005）。SLE患者MBD 2（r=-0.609，P < 0.0005）和MBD 4（r=-0.395，P=0.034）基因表达水平与甲基化指数呈负相关。MBD 2和MBD 4转录物过表达和与DNA甲基化指数的负相关性表明，这两种酶可能确实对SLE患者CD 4 + T细胞中观察到的全基因组DNA低甲基化具有直接和积极的作用。
Global DNA hypoinethylation in CD4+ T cells has been detected in systemic lupus erythematosus (SLE), and it seems to be linked to its pathogenesis. We investigated the relationship between overall DNA methylation and the expression of two methyl CpG-binding domain (MBD) proteins. DNA deoxymethylcytosine (d(m)C) content of purified CD4+ T cells from 29 SLE patients and 30 healthy controls was measured by means of an ELISA. Transcript levels of two methyl CpG-binding proteins (MBD2 and MBD4) were quantified by real-time RT-PCR. Association studies were also carried out with several laboratory parameters, as well as with the patients' clinical manifestations. SLE patients had significantly less CD4+ T cell DNA d(m)C content than controls (0.802 +/- 0.134 vs. 0.901 +/- 0.133; P=0.007). MBD2 and MBD4 mRNA levels were considerably higher in the patients' group: 0.975 +/- 0683 versus 0.604 +/- 0.614 (P=0.004) and 0.359 +/- 0.330 versus 0.092 +/- 0.169, respectively (P < 0.0005). It is interesting that SLE patients showed a negative correlation between methylation indices and MBD2 (r=-0.609, P < 0.0005) and MBD4 (r=-0.395, P=0.034) transcript levels. MBD2 and MBD4 transcript overexpression and inverse correlations with DNA methylation indices indicate that both enzymes may really have a direct and active role on the genome-wide DNA hypomethylation observed in CD4+ T cells from SLE patients.