慢性呼吸道上皮缺氧在粘液阻塞性肺病中通过粘液过度度加剧损伤
Yu Mikami1, Barbara R Grubb1, Troy D Rogers1
1Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.
Science translational medicine
|June 7, 2023
概括
慢性气道缺氧导致粘液过度产生,在肺部疾病中导致气道损伤. 这种缺氧促进了MUC5B粘液和吸收的增加,使粘液阻塞和呼吸道重塑在粘液阻塞性肺部疾病中恶化.
科学领域:
- 肺部医学 肺部医学
- 细胞生物学 细胞生物学
- 病理生理学 病理生理学
背景情况:
- 空气道上皮质依赖于吸入的空气获得氧气,与其他组织不同.
- 肺部疾病通常涉及粘液塞,异物或瘤的气道阻塞.
- 慢性阻塞性肺病 (COPD) 肺部粘液塞附近的气道上皮质是低氧的,但慢性低氧 (CH) 的影响是未知的.
研究的目的:
- 为了研究慢性缺氧 (CH) 对气道上皮质宿主防御功能的影响.
- 探索粘膜阻塞性肺病 (MOLDs) 中CH的基础分子机制.
主要方法:
- 来自MOLD和COVID-19患者的人类肺组织的分子特征.
- 在体外研究中使用培养的慢性缺氧气道上皮.
- 分析MUC5B的产生,体Na+和液体吸收以及基因表达 (RNA测序).
- RNA-in-situ杂交,以证实在人类肺组织中的发现.
主要成果:
- CH在呼吸道上皮质中诱导一种甘油性代谢状态.
- 低毒性表皮表皮显示MUC5B粘素的产生增加,通过依赖HIF1α/HIF2α的ENaC子单元上调调节增强的吸收.
- 这导致过度缩的粘液,使阻塞延续.
- 转录分析揭示了与呼吸道壁重塑,破坏和血管生成有关的变化.
结论:
- 慢性呼吸道上皮缺氧是MOLDs持续粘液积累的一个关键因素.
- 缺氧有助于呼吸道壁损伤和重塑.
- 准缺氧通路可能为MOLDs提供新的治疗策略.
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