Systemic lupus erythematosus (SLE), a complex polygenic autoimmune disease, is associated with increased complement activation. Complement factor H related protein 5 (CFHR5) may contribute to dysfunctional complement activation, thus predisposing to SLE. The expression levels of anti-dsDNA, C3 and CFHR5 in blood samples from 50 SLE patients and 50 healthy individuals were evaluated, and also their expression levels were measured in an MRL/lpr mouse model and control MRL/MPJ mice. The results showed that CFHR5 expression increased in SLE patients together with the increase of anti-dsDNA in comparison with the healthy control. Furthermore, CFHR5 expression was inversely correlated with C3, down-regulation of which was associated with worse SLE. Previous studies indicated that long noncoding RNA (lncRNA) regulates mRNA synthesis via microRNA (miRNA) inhibition. The present bioinformatics analysis revealed that the target miRNA (miR-222) was combined with both lncRNA MIAT and mRNA CFHR5. H&E staining of the kidney tissues of the MRL/lpr mice revealed that lncRNA MIAT, as a competitive inhibitor of miR-222, enhanced SLE by upregulating CFHR5 expression through the degradation of miR-222 in vivo. Thus, our study revealed for the first time the role of lncRNA MIAT in regulating CFHR5 expression in SLE in vivo and provided new insights into the role of lncRNA in regulation and complement function of SLE pathogenesis.

中文翻译：

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LncRNA MIAT通过通过miR-222降解上调CFHR5表达来增强系统性红斑狼疮

系统性红斑狼疮（SLE）是一种复杂的多基因自身免疫性疾病，与补体激活增加有关。补体因子H相关蛋白5（CFHR5）可能导致功能失调的补体激活，因此易患SLE。评价了来自50名SLE患者和50名健康个体的血液样品中抗dsDNA，C3和CFHR5的表达水平，并且还在MRL / lpr小鼠模型和对照MRL / MPJ小鼠中测量了它们的表达水平。结果表明，与健康对照相比，SLE患者CFHR5表达增加，同时抗dsDNA升高。此外，CFHR5表达与C3呈负相关，而C3的下调与较差的SLE有关。先前的研究表明，较长的非编码RNA（lncRNA）通过抑制microRNA（miRNA）调节mRNA的合成。目前的生物信息学分析表明，目标miRNA（miR-222）与lncRNA MIAT和mRNA CFHR5都结合了。对MRL / lpr小鼠肾脏组织的H＆E染色显示，作为miR-222竞争性抑制剂的lncRNA MIAT通过上调miHR-222的降解上调CFHR5表达来增强SLE。体内。因此，我们的研究首次揭示了lncRNA MIAT在体内调节SLE中CFHR5表达的作用，并为lncRNA在SLE发病机理的调节和补体功能中的作用提供了新的见解。