骨髓细胞中的HIF1α依赖性缺氧反应需要IRE1α
Gaëlle Mawambo1, Malika Oubaha1,2, Yusuke Ichiyama3
1Department of Biochemistry, Maisonneuve-Rosemont Hospital Research Centre, Université de Montréal, 5415 De L'Assomption Boulevard, Montréal, QC, H1T 2M4, Canada.
Journal of neuroinflammation
|June 21, 2023
概括
天生的免疫细胞通过IRE1α/XBP1通路适应低氧,这对于触发缺氧诱导因子 (HIF) -1α至关重要. 这种适应性调节炎症反应在条件,如无菌炎症.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
背景情况:
- 细胞适应缺氧和代谢压力对于受伤组织的免疫细胞功能至关重要.
- 缺氧诱导因子 (HIF) - 1α对于髓状细胞的炎症反应至关重要,调节糖解.
- 在炎症期间HIF1α激活的确切触发因素在很大程度上是未知的.
研究的目的:
- 调查因诺醇需要酶1α (IRE1α/XBP1) 轴在启动依赖HIF1α的炎症反应中的作用.
- 阐明先天免疫细胞适应低氧张力和代谢压力的机制.
- 确定IRE1α和HIF1α对无菌炎症病理血管生成的影响.
主要方法:
- 在髓状细胞中使用HIF1α和IRE1α的淘汰模型.
- 在低氧条件下分析细胞因子 (IL1β,IL6,VEGF-A) 的产生.
- 在无菌炎症视网膜血管生成模型中评估血管表型.
主要成果:
- IRE1α/XBP1轴是关键炎症类细胞因子的HIF1α依赖性产生所需的.
- 骨髓细胞中HIF1α或IRE1α的淘汰显著减少了病理性血管生成中的血管异常.
- ER应激通路与HIF1α一起,似乎共同调节免疫适应缺氧.
结论:
- IRE1α/XBP1通路是先天免疫细胞中HIF1α激活的关键上游调节器.
- 针对 IRE1α/HIF1α 轴可能为因缺氧和血管生成而导致的炎症性疾病提供治疗策略.
- 免疫细胞适应低氧气需要ER应激和HIF1α信号之间的协调相互作用.
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