Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, University of South China, Hengyang 421001, Hunan, China.
Biochimie. 2012 Dec;94(12):2749-55. doi: 10.1016/j.biochi.2012.08.018. Epub 2012 Aug 31.
LPL (lipoprotein lipase) is a rate-limiting enzyme involved in the hydrolysis of triglycerides. Previous studies have shown that microRNA (miR)-467b regulates hepatic LPL expression and plays a role in the progression of steatosis or abnormal lipid retention in obese mice. Macrophage-derived LPL has been shown to promote atherosclerosis. However, if miR-476b influences macrophage LPL expression and the subsequent effects are unknown. Here, we utilized oxLDL-treatment RAW 264.7 macrophages that were transfected with miR-467b mimics or inhibitors to investigate the potential roles of macrophage miR-476b. We found that miR-467b significantly decreased lipid accumulation and IL-6, IL-1β, TNF-α and MCP-1 secretions. Furthermore, our studies suggested an additional explanation for the regulatory mechanism of miR-467b on its functional target, LPL in RAW 264.7 macrophages. Thus, our findings indicate that miR-467b may regulate lipid accumulation and proinflammatory cytokine secretion in oxLDL-stimulated RAW 264.7 macrophages by targeting the LPL gene.
脂蛋白脂肪酶(LPL)是一种限速酶,参与甘油三酯的水解。先前的研究表明,微小 RNA(miR)-467b 调节肝 LPL 表达,并在肥胖小鼠的脂肪变性或异常脂质蓄积进展中发挥作用。巨噬细胞来源的 LPL 已被证明可促进动脉粥样硬化。然而,如果 miR-476b 影响巨噬细胞 LPL 表达,其后续作用尚不清楚。在这里,我们利用 oxLDL 处理转染 miR-467b 模拟物或抑制剂的 RAW 264.7 巨噬细胞,研究巨噬细胞 miR-476b 的潜在作用。我们发现 miR-467b 可显著减少脂质积累和 IL-6、IL-1β、TNF-α 和 MCP-1 的分泌。此外,我们的研究为 miR-467b 对 RAW 264.7 巨噬细胞中其功能靶标 LPL 的调节机制提供了另一种解释。因此,我们的研究结果表明,miR-467b 可能通过靶向 LPL 基因来调节 oxLDL 刺激的 RAW 264.7 巨噬细胞中的脂质积累和促炎细胞因子分泌。