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首页> 外文期刊>Aging cell. >miR-195-3p alleviates homocysteine-mediated atherosclerosis by targeting IL-31 through its epigenetics modifications
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miR-195-3p alleviates homocysteine-mediated atherosclerosis by targeting IL-31 through its epigenetics modifications

机译:miR-195-3p通过其外观遗传修饰靶向IL-31,减轻了同型半胱氨酸介导的动脉粥样硬化

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Atherosclerosis is a serious age-related disease, which has a tremendous impact on health care globally. Macrophage inflammation is crucial for the initiation and progression of atherosclerosis, and microRNAs (miRNAs) recently have emerged as potent modulators of inflammation, while the underlying mechanisms of its involvement in homocysteine (Hcy)-mediated macrophage inflammation of atherosclerosis remain largely unknown. Here, we demonstrated that elevated Hcy inhibits the expression of miR-195-3p, which in turn enhances IL-31 expression and thereby causes the secretion of macrophages pro-inflammatory factors IL-1β, IL-6 and TNF-α and accelerate atherosclerosis. Furthermore, we identified that Hcy can induce DNA hypermethylation and H3K9 deacetylation of miR-195-3p promoter due to the increased the binding of DNMT3a and HDAC11 at its promoter. More importantly, Sp1 interacts with DNMT3a suppressed the binding of HDAC11 at miR-195-3p promoter and promoted its transcription. In summary, our results revealed a novel mechanism that transcriptional and epigenetic regulation of miR-195-3p inhibits macrophage inflammation through targeting IL-31, which provides a candidate diagnostic marker and novel therapeutic target in cardiovascular diseases induced by Hcy.
机译:动脉粥样硬化是一种严重的年龄相关疾病,对全球的医疗保健产生了巨大影响。巨噬细胞炎症对于动脉粥样硬化的启动和进展至关重要,MicroRNA(miRNA)最近被出现为炎症的有效调节剂,而其参与同型心囊炎(Hcy)介导的动脉粥样硬化的巨噬细胞炎症的潜在机制仍然很大程度上是未知的。在这里,我们证明升高的Hcy抑制miR-195-3p的表达,这反过来增强了IL-31表达,从而导致巨噬细胞的分泌促炎素IL-1β,IL-6和TNF-α并加速动脉粥样硬化。此外,我们认为HCY可以诱导MIR-195-3P启动子的DNA高甲基化和H3K9脱乙酰化由于其启动子在其启动子上的结合增加。更重要的是,SP1与DNMT3A相互作用抑制了MIR-195-3P启动子HDAC11的结合,并促进了其转录。总之,我们的结果揭示了一种新的机制,MiR-195-3P的转录和表观遗传调节通过靶向IL-31抑制巨噬细胞炎症,其为Hcy诱导的心血管疾病提供了候选诊断标志物和新的治疗靶标。

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