Department of Medicine, National Jewish Health, 1400 Jackson Street, K736A, Denver, CO 80206, USA.
Am J Respir Cell Mol Biol. 2012 Oct;47(4):395-404. doi: 10.1165/rcmb.2012-0100TR. Epub 2012 May 31.
Acute lung injury (ALI) is a syndrome marked by increased permeability across the pulmonary epithelium resulting in pulmonary edema. Recent evidence suggests that members of the human epidermal growth factor receptor (HER) family are activated in alveolar epithelial cells during ALI and regulate alveolar epithelial barrier function. These tyrosine kinase receptors, which also participate in the pathophysiology of pulmonary epithelial malignancies, regulate cell growth, differentiation, and migration as well as cell-cell adhesion, all processes that influence epithelial injury and repair. In this review we outline mechanisms of epithelial injury and repair in ALI, activation patterns of this receptor family in pulmonary epithelial cells as a consequence injury, how receptor activation alters alveolar permeability, and the possible intracellular signaling pathways involved. Finally, we propose a theoretical model for how HER-mediated modulation of alveolar permeability might affect lung injury and repair. Understanding how these receptors signal has direct therapeutic implications in lung injury and other diseases characterized by altered epithelial barrier function.
急性肺损伤（ALI）是一种以肺上皮通透性增加为特征的综合征，导致肺水肿。最近的证据表明，在 ALI 期间，人表皮生长因子受体（HER）家族的成员在肺泡上皮细胞中被激活，并调节肺泡上皮屏障功能。这些酪氨酸激酶受体也参与肺上皮恶性肿瘤的病理生理学，调节细胞生长、分化和迁移以及细胞-细胞黏附，所有这些过程都影响上皮损伤和修复。在这篇综述中，我们概述了 ALI 中上皮损伤和修复的机制、该受体家族在肺上皮细胞中的激活模式作为损伤的结果、受体激活如何改变肺泡通透性，以及可能涉及的细胞内信号通路。最后，我们提出了一个理论模型，说明 HER 介导的肺泡通透性调节如何影响肺损伤和修复。了解这些受体如何信号具有直接的治疗意义，可用于肺损伤和其他以改变上皮屏障功能为特征的疾病。
