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通过母酶介导的PAR2激活在低氧条件下驱动单细胞到巨细胞的分化和两极化

Arpana Singh¹, Avinandan Bhoumick², Prosenjit Sen²

¹Abramson Cancer Center and Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

The FEBS journal

|February 27, 2025

概括

缺氧驱动单细胞分化到M1巨细胞通过母酶和PAR2激活. 然而,长时间的缺氧将偏向转移到M2,揭示了瘤微环境中的动态免疫反应.

科学领域:

免疫学免疫学免疫学
细胞生物学细胞生物学
癌症研究癌症研究

背景情况:

缺氧是瘤微环境 (TME) 中影响免疫细胞行为的一个关键因素.
巨细胞两极分化 (M1/M2) 对抗瘤免疫和瘤进展至关重要.

研究的目的:

为了研究缺氧在调节巨细胞极化中的作用.
确定参与低氧诱导的巨细胞分化中的关键分子媒介.

主要方法:

使用的单细胞细胞系 (THP1) 和外周血液单核细胞 (PBMC).
暴露细胞在不同的低氧条件下,并测量了乳酸积累.
评估了母质酶 (TMPRSS2) 和蛋白酶激活受体2 (PAR2) 的表达和激活.
分析了包括AKT2-NF-κβ和miR155表达在内的下游信号通路.
监测的巨细胞极化标志物 (M1/M2).

主要成果:

缺氧诱导了母质酶激活和随后的PAR2在单细胞中的表达.
在缺氧下,乳酸积累 (≥10 mM) 通过AKT2-NF-κβ和miR155上调驱动M1巨细胞偏振.
持续的缺氧 (≥48h,25 mM乳酸) 抑制了母质酶的激活,导致M2极化.
马特里酶在低氧瘤微环境中作为巨细胞两极分化的关键调节剂.

结论:

孕酶-PAR2轴是低氧驱动的巨细胞两极分化的关键调解者.
这项研究揭示了长期缺氧下,巨细胞极化从M1到M2的时间切换.
这些发现为癌症治疗中的免疫调节策略提供了潜在的目标.

关键词:

M1 和 M2 的两极化.在PAR2中,PAR2是PAR2的一部分.不同化的差异化差异化.巨细胞是一个巨细胞.它们是 matriptase 的基因.

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