内质网（ER）应激与纤维化疾病（包括特发性肺纤维化（IPF））的发生和发展有关。早在15年前IPR的发病机理中就发现了内质网应激，这是由于发现了表面活性剂蛋白C的致病突变所致，该突变导致II型肺泡上皮细胞（AEC）的基因产物折叠错误。内质网应激和未折叠的蛋白反应（UPR）通过调节AEC凋亡，上皮-间质转化，成肌纤维细胞分化和M2巨噬细胞极化与肺纤维化有关。尽管在了解IPF和许多慢性纤维化疾病中ER压力的原因和后果方面取得了进展，需要进一步的研究来确定在重要细胞类型中诱导内质网应激的关键因素，并确定关键的下游过程和介导内质网应激相关表型的效应分子。这篇综述讨论了在肺中诱发ER应激的潜在原因，以及在单个细胞类型（AEC，成纤维细胞和巨噬细胞）的背景下将ER应激与纤维化联系起来的当前证据。随着我们对内质网应激与肺纤维化之间关系的理解不断发展，未来的研究将研究调节UPR途径以取得治疗益处的新策略。成纤维细胞和巨噬细胞。随着我们对内质网应激与肺纤维化之间关系的理解不断发展，未来的研究将研究调节UPR途径以取得治疗益处的新策略。成纤维细胞和巨噬细胞。随着我们对内质网应激与肺纤维化之间关系的理解不断发展，未来的研究将研究调节UPR途径以取得治疗益处的新策略。

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Endoplasmic reticulum (ER) stress is associated with development and progression of fibrotic diseases, including idiopathic pulmonary fibrosis (IPF). ER stress was first implicated in the pathogenesis of IPF >15 years ago with the discovery of disease-causing mutations in surfactant protein C, which result in a misfolded gene product in type II alveolar epithelial cells (AECs). ER stress and the unfolded protein response (UPR) have been linked to lung fibrosis through regulation of AEC apoptosis, epithelial-mesenchymal transition, myofibroblast differentiation, and M2 macrophage polarization. Although progress has been made in understanding the causes and consequences of ER stress in IPF and a number of chronic fibrotic disorders, further studies are needed to identify key factors that induce ER stress in important cell types and define critical down-stream processes and effector molecules that mediate ER stress-related phenotypes. This review discusses potential causes of ER stress induction in the lungs and current evidence linking ER stress to fibrosis in the context of individual cell types: AECs, fibroblasts, and macrophages. As our understanding of the relationship between ER stress and lung fibrosis continues to evolve, future studies will examine new strategies to modulate UPR pathways for therapeutic benefit.