Decreased Peripheral Blood ALKBH5 Correlates with Markers of Autoimmune Response in Systemic Lupus Erythematosus
Decreased Peripheral Blood ALKBH5 Correlates with Markers of Autoimmune Response in Systemic Lupus Erythematosus
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外周血 ALKBH5 降低与系统性红斑狼疮自身免疫反应标志物相关
DOI：
10.1155/2020/8193895
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发表时间：
2020-06-25
期刊：
影响因子：
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通讯作者：
Li, Junming
中科院分区：
文献类型：
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作者：
Luo, Qing;Fu, Biqi;Li, Junming
虽然已经证实DNA和组蛋白的表观遗传修饰参与了系统性红斑狼疮(SLE)的发病，但目前还没有研究探讨RNA中的N6-甲基腺苷(M6A)修饰是否参与了SLE的发病。本研究采用定量逆转录-聚合酶链式反应(qRT-PCR)方法检测外周血中m6A“编写者”(METTL3、MTEEL14和WTAP)、“ERASERS”(FTO和ALKBH5)和“Readers”(YTHDF2)的mRNA水平。结果表明，SLE患者外周血中METTL3、WTAP、FTO、ALKBH5和YTHDF2的mRNA水平显著降低。SLE患者ALKBH5mRNA水平与抗双链DNA抗体、抗核小体、皮疹和溃疡有关。多因素Logistic回归分析显示，外周血ALKBH5mRNA水平是系统性红斑狼疮的危险因素(P<；0.001)。此外，我们的结果还表明，SLE患者m6A“编写器”(METTL3和WTAP)、“擦除器”(FTO和ALKBH5)和“读取器”(YTHDF2)之间存在正相关。提示SLE患者外周血中ALKBH5的表达水平可能参与了SLE的发病机制。
Although it has been proved that the epigenetic modification of DNA and histones is involved in the pathogenesis of systemic lupus erythematosus (SLE), there is no study to explore whether the modification of N6-methyladenosine (m6A) in RNA is involved. In this study, the mRNA levels of m6A “writers” (METTL3, MTEEL14, and WTAP), “erasers” (FTO and ALKBH5), and “readers” (YTHDF2) in peripheral blood were determined by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The results demonstrated that the mRNA levels of METTL3, WTAP, FTO, ALKBH5, and YTHDF2 in peripheral blood from SLE patients were significantly decreased. The levels of ALKBH5 mRNA in SLE patients were associated with anti-dsDNA, antinucleosome, rash, and ulceration. Multivariate logistic regression analysis showed that the level of ALKBH5 mRNA in peripheral blood is a risk factor of SLE (P < 0.001). Moreover, our results suggested that there was a positive correlation between m6A“writers” (METTL3 and WTAP), “erasers” (FTO and ALKBH5), and “readers” (YTHDF2) in SLE patients. This study suggests that the mRNA level of ALKBH5 in peripheral blood may be involved in the pathogenesis of SLE.