在喘患者的呼吸道上皮质中观察到升高的PLAUR,阻塞改善了屏障完整性
Michael A Portelli1, Sangita Bhaker1, Vincent Pang2
1Centre for Respiratory Research, NIHR Respiratory Biomedical Research Centre, School of Medicine, Biodiscovery Institute, University Park, University of Nottingham, Nottingham, UK.
Clinical and translational allergy
|October 25, 2023
概括
在喘患者中,泌尿酸酶等离子体激活受体 (uPAR) 的升高与呼吸道上皮屏障的削弱相关. 阻止UPAR功能可以改善屏障完整性,这表明UPAR是喘治疗的治疗点.
科学领域:
- 呼吸系统医学 呼吸系统医学
- 细胞生物学 细胞生物学
- 免疫学 免疫学 免疫学
背景情况:
- 泌尿酸酶等离子体激活剂受体 (uPAR) 表达在喘患者的呼吸道上皮质中增加.
- 尤帕在喘发病的具体作用及其作为治疗点的潜力尚未完全理解.
研究的目的:
- 研究喘患者的人类支气管上皮细胞 (HBEC) 中的UPAR表达.
- 为了确定 uPAR 和上皮屏障功能之间的关系.
- 探索不同PAR异型的功能影响.
主要方法:
- 来自喘患者的HBEC和在空气液体接口 (ALI) 的量化UPAR水平.
- 评估了使用体电阻和电池阻抗传感器的屏障特性,包括PUPAR阻断抗体的影响.
- 利用转录学分析了表达过度的UPAR异型 (muPAR,scuPAR,ssuPAR) 的功能影响.
主要成果:
- 喘患者的HBECs表现出升高的UPAR表达,表明细胞内在变化.
- 在2D和ALI培养物中,可溶性UPAR水平与上皮屏障完整性呈反相关性.
- 阻断UPAR-整合素相互作用导致皮质屏障形成的改善.
- 过度表达UPAR异型导致了最小的转录基因变化.
结论:
- 这项研究澄清了喘,UPAR和上皮屏障功能障碍之间的联系.
- 循环UPAR的升高有助于表皮屏障受损,这是喘的一个特征.
- uPAR代表了一种潜在的治疗点,用于改善喘中的呼吸道屏障功能.
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