Cambridge Institute for Medical Research (CIMR), University of Cambridge, UK.
FEBS J. 2019 Jan;286(2):322-341. doi: 10.1111/febs.14381. Epub 2018 Jan 22.
Protein misfolding within the endoplasmic reticulum (ER stress) can be a cause or consequence of pulmonary disease. Mutation of proteins restricted to the alveolar type II pneumocyte can lead to inherited forms of pulmonary fibrosis, but even sporadic cases of pulmonary fibrosis appear to be strongly associated with activation of the unfolded protein response and/or the integrated stress response. Inhalation of smoke can impair protein folding and may be an important cause of pulmonary ER stress. Similarly, tissue hypoxia can lead to impaired protein homeostasis (proteostasis). But the mechanisms linking smoke and hypoxia to ER stress are only partially understood. In this review, we will examine the role of ER stress in the pathogenesis of lung disease by focusing on fibrosis, smoke, and hypoxia.
内质网（ER）中的蛋白质错误折叠可能是肺部疾病的原因或后果。局限于肺泡 II 型上皮细胞的蛋白质突变可导致遗传性肺纤维化，但即使是散发性肺纤维化病例，似乎也与未折叠蛋白反应和/或综合应激反应的激活密切相关。烟雾吸入会损害蛋白质折叠，可能是导致肺 ER 应激的重要原因。同样，组织缺氧也会导致蛋白质平衡（蛋白稳态）受损。但是，将烟雾和缺氧与 ER 应激联系起来的机制还只是部分被理解。在这篇综述中，我们将通过关注纤维化、烟雾和缺氧来研究 ER 应激在肺部疾病发病机制中的作用。
