PARP7保护肺上皮屏障免受各种环境威胁
Devon Jeltema1, Kun Yang1, Joshua J Baty2
1Department of Immunology, University of Texas Southwestern Medical Center, Dallas, TX 75390.
概括
聚-ADP-ribose聚合酶7 (PARP7) 对肺部健康至关重要. 失去PARP7会损害肺屏障的完整性,增加受伤和疾病的易感性,对肺部疾病有影响.
科学领域:
- 肺部医学 肺部医学
- 细胞生物学 细胞生物学
- 分子毒理学 分子毒理学
背景情况:
- 聚-ADP-ribose聚合酶 (PARP) 家族蛋白调节关键细胞功能.
- 虽然PARP抑制剂用于癌症治疗,但大多数PARP的生理作用和潜在的不良影响仍然基本上未被描述.
- PARP7在肺生理中的具体作用尚不清楚.
研究的目的:
- 为了研究PARP7在肺中的生理功能.
- 确定PARP7丧失或抑制对肺上皮质屏障完整性和对环境挑战的反应的影响.
- 阐明PARP7在肺中的功能背后的分子机制.
主要方法:
- 使用PARP7缺乏的小鼠模型来评估易受化学诱导的肺损伤 (扩散膜出血) 和自身免疫性疾病 (狼) 的敏感性.
- 使用单核RNA测序 (snRNA-seq) 来分析肺组织中的基因表达模式.
- 对人类支气管上皮细胞进行了空气-液体接口 (ALI) 培养实验,以评估在PARP7抑制和暴露于香烟烟雾或细菌感染后的屏障功能.
主要成果:
- 在小鼠中,PARP7 缺乏增加了对扩散性气囊出血和原始性狼的敏感性.
- snRNA-seq揭示了PARP7在膜I型细胞中的选择性表达,并表明PARP7的损失损害了上皮屏障的完整性,导致免疫细胞透.
- 人类支气管上皮细胞中PARP7抑制增加了暴露于香烟烟雾或细菌感染后的屏障透性.
- 从机理上讲,PARP7准烯碳化合物受体 (AHR),该受体调解了对香烟烟雾的反应,包括奥克卢丁损失和异生物代谢和炎症基因的改变表达.
结论:
- PARP7在维持肺上皮质屏障完整性方面发挥着至关重要的作用.
- PARP7的功能对于保护肺部免受烟雾和感染等环境污辱至关重要.
- 这些发现突出了PARP7作为肺健康的关键调节剂,并建议对管理肺部疾病和指导PARP7抑制剂治疗的潜在临床影响.
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