Background Ubiquitination-mediated M1/M2 macrophage polarization plays important roles in the pathogenesis of immune disease. However, the regulatory mechanism of ubiquitination during M1/M2 macrophage polarization following intracerebral hemorrhage (ICH) has not been well studied. Methods In the experiment, macrophages were administered with erythrocyte lysates, and then miR-494-, Nrdp1-, and M1/M2-related markers were analyzed. Brain inflammatory response, brain edema, and neurological functions of ICH mice were also assessed. Results We found that miR-494 levels increased while Nrdp1 levels decreased in macrophages after ICH. We also demonstrated that miR-494 inhibited Nrdp1 expression by directly binding its 3'-untranslated region. MiR-494 attenuated C/EBP-β activation and downstream proinflammatory factor production. Upregulation of Nrdp1 in macrophages significantly promoted M2 macrophage polarization via ubiquitinating and activating C/EBP-β. Moreover, the results indicated that miR-494 could enhance M1 macrophage polarization, promote brain edema, and impair neurological functions in ICH mice. Conclusions Taken together, our results demonstrated that Nrdp1 contributed to M1/M2 macrophage polarization and neuroinflammation via ubiquitination and activation of C/EBP-β in ICH. miR-494 may provide a promising therapeutic clue for ICH.

中文翻译：

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在 ICH 小鼠模型中，miRNA-494 通过 Nrdp1 增强 M1 巨噬细胞极化。

背景泛素化介导的 M1/M2 巨噬细胞极化在免疫疾病的发病机制中起重要作用。然而，脑出血 (ICH) 后 M1/M2 巨噬细胞极化过程中泛素化的调节机制尚未得到很好的研究。方法在实验中，巨噬细胞与红细胞裂解物一起给药，然后分析miR-494-、Nrdp1-和M1/M2相关标志物。还评估了 ICH 小鼠的脑炎症反应、脑水肿和神经功能。结果 我们发现 ICH 后巨噬细胞中 miR-494 水平升高而 Nrdp1 水平降低。我们还证明了 miR-494 通过直接结合其 3'-非翻译区来抑制 Nrdp1 的表达。MiR-494 减弱 C/EBP-β 活化和下游促炎因子的产生。巨噬细胞中 Nrdp1 的上调通过泛素化和激活 C/EBP-β 显着促进 M2 巨噬细胞极化。此外，结果表明 miR-494 可以增强 ICH 小鼠的 M1 巨噬细胞极化，促进脑水肿，并损害神经功能。结论 综上所述，我们的结果表明 Nrdp1 通过泛素化和激活 ICH 中的 C/EBP-β 促进 M1/M2 巨噬细胞极化和神经炎症。miR-494 可能为 ICH 提供有希望的治疗线索。我们的研究结果表明，Nrdp1 通过泛素化和激活 ICH 中的 C/EBP-β 促进 M1/M2 巨噬细胞极化和神经炎症。miR-494 可能为 ICH 提供有希望的治疗线索。我们的研究结果表明，Nrdp1 通过泛素化和激活 ICH 中的 C/EBP-β 促进 M1/M2 巨噬细胞极化和神经炎症。miR-494 可能为 ICH 提供有希望的治疗线索。