间质性肺疾病（ILD）代表一大类以慢性炎症和肺纤维化为特征的疾病，治疗选择有限。在几个导致家族性ILD的常染色体显性遗传的致病基因中，SFTPC基因的BRICHOS结构域突变导致其前蛋白错误折叠，引起蛋白在内质网中的积累和内质网应激。通过在HEK293细胞中使用这两种表型进行筛选系统，并使用经过患者诱导多能干细胞（iPSCs）分化为肺泡上皮2型细胞（AT2）细胞的评估，我们确定了丹参酮（CPT）作为一种潜在的ILD治疗药物。CPT降低了A549和HEK293细胞中突变SFTPC过表达引起的细胞死亡，并改善了具有SFTPC突变的来源于iPSCs的成纤维依赖型肺泡器官样体中的布洛霉素引起的基质收缩。CPT以及这种筛选策略可应用于异常蛋白折叠相关的ILD和其他蛋白质错误折叠疾病。©2023年作者们。

Interstitial lung disease (ILD) represents a large group of diseases characterized by chronic inflammation and fibrosis of the lungs, for which therapeutic options are limited. Among several causative genes of familial ILD with autosomal dominant inheritance, the mutations in the BRICHOS domain of SFTPC cause protein accumulation and endoplasmic reticulum stress by misfolding its proprotein. Through a screening system using these two phenotypes in HEK293 cells and evaluation using alveolar epithelial type 2 (AT2) cells differentiated from patient-derived induced pluripotent stem cells (iPSCs), we identified Cryptotanshinone (CPT) as a potential therapeutic agent for ILD. CPT decreased cell death induced by mutant SFTPC overexpression in A549 and HEK293 cells and ameliorated the bleomycin-induced contraction of the matrix in fibroblast-dependent alveolar organoids derived from iPSCs with SFTPC mutation. CPT and this screening strategy can apply to abnormal protein-folding-associated ILD and other protein-misfolding diseases.© 2023 The Authors.