Ion channel Piezo1 activation promotes aerobic glycolysis in macrophages.
Ion channel Piezo1 activation promotes aerobic glycolysis in macrophages.
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离子通道 Piezo1 激活促进巨噬细胞有氧糖酵解
DOI：
10.3389/fimmu.2022.976482
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发表时间：
2022
影响因子：
7.3
通讯作者：
中科院分区：
文献类型：
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改变微环境硬度是炎症的标志。它被巨噬细胞中机械激活的阳离子通道Piezo 1感知，以诱导随后的免疫应答。然而，机械敏感信号塑造巨噬细胞代谢状态和调节免疫反应的机制仍不清楚。我们发现，Piezo 1缺陷的巨噬细胞表现出减少有氧糖酵解在休息或脂多糖（LPS）刺激的巨噬细胞与受损的LPS诱导的炎症细胞因子的分泌在体外。此外，预处理与Piezo 1激动剂，Yoda 1，或循环静水压力（CHP）上调糖酵解活性和增强LPS诱导的炎症细胞因子的分泌。Piezo 1缺陷小鼠对葡聚糖硫酸钠（DSS）诱导的结肠炎不太敏感，而Yoda 1治疗加重了结肠炎。从机制上讲，我们发现Piezo 1激活通过Ca 2+诱导的CaMKII-HIF 1 α轴促进有氧糖酵解。因此，我们的研究表明，Piezo 1介导的机械敏感信号Piezo 1可以增强有氧糖酵解，促进LPS诱导的巨噬细胞免疫反应。
Altered microenvironmental stiffness is a hallmark of inflammation. It is sensed by the mechanically activated cation channel Piezo1 in macrophages to induce subsequent immune responses. However, the mechanism by which the mechanosensitive signals shape the metabolic status of macrophages and tune immune responses remains unclear. We revealed that Piezo1-deficient macrophages exhibit reduced aerobic glycolysis in resting or liposaccharide (LPS)-stimulated macrophages with impaired LPS-induced secretion of inflammatory cytokines in vitro. Additionally, pretreatment with the Piezo1 agonist, Yoda1, or cyclical hydrostatic pressure (CHP) upregulated glycolytic activity and enhanced LPS-induced secretion of inflammatory cytokines. Piezo1-deficient mice were less susceptible to dextran sulfate sodium (DSS)-induced colitis, whereas Yoda1 treatment aggravated colitis. Mechanistically, we found that Piezo1 activation promotes aerobic glycolysis through the Ca2+-induced CaMKII-HIF1α axis. Therefore, our study revealed that Piezo1-mediated mechanosensitive signals Piezo1 can enhance aerobic glycolysis and promote the LPS-induced immune response in macrophages.