Familial Mediterranean fever-related miR-197-3p targets IL1R1 gene and modulates inflammation in monocytes and synovial fibroblasts.
Familial Mediterranean fever-related miR-197-3p targets IL1R1 gene and modulates inflammation in monocytes and synovial fibroblasts.
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DOI：
10.1038/s41598-020-80097-4
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发表时间：
2021-01-12
影响因子：
4.6
通讯作者：
Balci-Peynircioglu B
中科院分区：
文献类型：
--
作者：
Akkaya-Ulum YZ;Akbaba TH;Tavukcuoglu Z;Chae JJ;Yilmaz E;Ozen S;Balci-Peynircioglu B
家族性地中海热（FMF）;是一种常染色体Reconstructive遗传性自身炎症性疾病，由地中海热（MEFV）基因突变引起。最近的研究表明，表观遗传控制机制，特别是非编码RNA，可能在自身炎症的发病机制中发挥作用。microRNA（miRNAs）是一类在转录后水平调控宿主基因表达的小分子非编码RNA。FMF疾病的表型异质性表明FMF可能不是单基因疾病，表明表观遗传因素可能影响表型呈现。在这里，我们通过使用炎症相关功能测定来检查miR-197 - 3p的潜在抗炎作用，miR-197 - 3p是FMF患者中差异表达的miRNA。我们监测了重要细胞因子的基因表达水平，并对IL-1 β分泌、caspase-1活化、凋亡测定和细胞迁移测定进行了功能研究。这些实验用于评估前-miR-197转染后炎症的不同阶段。进行抗miR-197转染以测试相反的效果。3 ′ UTR荧光素酶活性测定用于目的基因的研究。我们通过炎症相关功能测定获得的结果证明了miR-197 - 3p在不同细胞类型（滑膜成纤维细胞、单核细胞、巨噬细胞）中的抗炎作用。3 ′ UTR荧光素酶活性检测显示，miR-197 - 3p可直接与IL-1 β受体I型（IL 1R1）基因结合，IL 1R1基因是炎症通路的关键分子之一。本研究为进一步了解miR-197 - 3p在自身炎症过程中的作用提供了理论依据。定义关键的miRNAs可以指导医学界在自身炎症性疾病中使用更个性化的药物。
Familial Mediterranean fever (FMF); is an autosomal recessively inherited autoinflammatory disease caused by the mutations in the Mediterranean Fever (MEFV) gene. Recent studies have shown that epigenetic control mechanisms, particularly non-coding RNAs, may play a role in the pathogenesis of autoinflammation. microRNAs (miRNAs) are small non-coding RNAs that play critical roles in regulating host gene expression at the post-transcriptional level. The phenotypic heterogeneity of FMF disease suggests that FMF may not be a monogenic disease, suggesting that epigenetic factors may affect phenotypic presentation. Here we examined the potential anti-inflammatory effect of miR-197-3p, which is a differentially expressed miRNA in FMF patients, by using inflammation related functional assays. We monitored gene expression levels of important cytokines, as well as performed functional studies on IL-1β secretion, caspase-1 activation, apoptosis assay, and cell migration assay. These experiments were used to evaluate the different stages of inflammation following pre-miR-197 transfection. Anti-miR-197 transfections were performed to test the opposite effect. 3′UTR luciferase activity assay was used for target gene studies. Our results obtained by inflammation-related functional assays demonstrated an anti-inflammatory effect of miR-197-3p in different cell types (synovial fibroblasts, monocytes, macrophages). 3′UTR luciferase activity assay showed that miR-197-3p directly binds to the interleukin-1beta (IL-1β) receptor, type I (IL1R1) gene, which is one of the key molecules of the inflammatory pathways. This study may contribute to understand the role of miR-197-3p in autoinflammation process. Defining the critical miRNAs may guide the medical community in a more personalized medicine in autoinflammatory diseases.
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