Mitochondrial dysfunction is associated with macrophage damage, but the role of mitochondrial fission in macrophage cholesterol metabolism is not fully understood. In this study, we explored the influences of miR-9 and mitochondrial fission on macrophage viability and cholesterol metabolism. Macrophages were incubated with oxidized low-density lipoprotein (ox-LDL) in vitro, after which mitochondrial fission, cell viability, and cholesterol metabolism were examined using qPCR, ELISAs, and immunofluorescence. ox-LDL treatment significantly increased Drp1-associated mitochondrial fission. Transfection of Drp1 siRNA significantly reduced cell death, attenuated oxidative stress, and inhibited inflammatory responses in ox-LDL-treated macrophages. Interestingly, inhibition of Drp1-related mitochondrial fission also improved cholesterol metabolism by balancing the transcription of cholesterol influx/efflux enzymes. We also found that miR-9 was downregulated in ox-LDL-treated macrophages, and administration of a miR-9 mimic decreased Drp1 transcription and mitochondrial fission, as well as its effects. These results indicate that signaling via the novel miR-9/Drp1/mitochondrial fission axis is a key determinant of macrophage viability and cholesterol metabolism.

中文翻译：

---

氧化 LDL 通过激活 miR-9/Drp1/线粒体裂变信号通路破坏代谢并抑制巨噬细胞存活

线粒体功能障碍与巨噬细胞损伤有关，但线粒体裂变在巨噬细胞胆固醇代谢中的作用尚不完全清楚。在这项研究中，我们探讨了 miR-9 和线粒体裂变对巨噬细胞活力和胆固醇代谢的影响。在体外将巨噬细胞与氧化低密度脂蛋白 (ox-LDL) 一起孵育，然后使用 qPCR、ELISA 和免疫荧光检查线粒体裂变、细胞活力和胆固醇代谢。ox-LDL 治疗显着增加了 Drp1 相关的线粒体分裂。Drp1 siRNA 的转染显着减少了 ox-LDL 处理的巨噬细胞的细胞死亡、减轻氧化应激并抑制炎症反应。有趣的是，抑制 Drp1 相关的线粒体裂变还可以通过平衡胆固醇流入/流出酶的转录来改善胆固醇代谢。我们还发现 ox-LDL 处理的巨噬细胞中 miR-9 下调，并且 miR-9 模拟物的施用减少了 Drp1 转录和线粒体裂变及其影响。这些结果表明，通过新型 miR-9/Drp1/线粒体裂变轴发出的信号是巨噬细胞活力和胆固醇代谢的关键决定因素。