减少的化对上皮质完整性产生影响,并增加了COPD的风险
Carter Swaby1, Bonnie Yeung-Luk2, Shreeti Thapa3
1Department of Chemical and Biomolecular Engineering, Johns Hopkins Whiting School of Engineering, Johns Hopkins University, Baltimore, Maryland, 21218, USA.
bioRxiv : the preprint server for biology
|November 14, 2023
概括
基转移酶-2 (FUT2) 对慢性阻塞性肺病 (COPD) 中的上皮屏障功能产生影响. FUT2增强了E-cadherin键,改善了肺上皮质的完整性,并可能为COPD提供一个新的治疗点.
科学领域:
- 肺部医学 肺部医学
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
背景情况:
- 慢性阻塞性肺病 (COPD) 是一种主要的全球健康问题,其特点是表皮损伤.
- 目前尚不完全了解COPD病原发生的精确机制.
- 乙素对上皮质完整性至关重要,并与COPD有关.
研究的目的:
- 研究fucosyltransferase-2 (FUT2) 在COPD病变发生过程中的作用.
- 阐明FUT2影响表皮屏障功能的分子机制.
- 探索FUT2作为COPD潜在的治疗点.
主要方法:
- 对COPD队列 (SPIROMICS,COPDgene) 的分析以确定遗传关联.
- 马尔迪-托夫分析以评估FUT2介导的E-cadherin可化.
- 原子力显微镜用于测量E-cadherin键强度.
- 使用Fut2淘汰赛小鼠和COPD衍生的上皮细胞的研究.
主要成果:
- 在COPD患者中,FUT2中的一种多态性被确定为E-cadherin的trans-pQTL.
- FUT2增加了E-cadherin的终端化,加强了细胞-细胞结合,并改善了上皮单层完整性.
- 在小鼠中Fut2缺乏会损害上皮质的完整性,并增加对肺和纤维化的敏感性.
- FUT2 影响细胞增殖和膜类型2 细胞分化.
结论:
- 在维持肺上皮质屏障功能方面,FUT2起着至关重要的作用.
- 对E-cadherin的FUT2-依赖的翻译后修饰代表了COPD病理学的新机制.
- FUT2调制是COPD的潜在治疗策略.
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