Abstract

Pulmonary fibrosis is caused by the interplay between genetic and environmental factors. Recent studies have revealed various genes associated with idiopathic pulmonary fibrosis, as well as the causative genes for familial pulmonary fibrosis. Although increased death or dysfunction of type 2 alveolar epithelial (AT2) cells has been detected in lung specimens from pulmonary fibrosis patients, it remains unclear whether and how AT2 cell death or dysfunction is responsible for the progression of pulmonary fibrosis. A recent study showed that increased AT2 cell necroptosis is the initial event in pulmonary fibrosis by analyzing patients with familial pulmonary fibrosis and an animal model that harbors the same mutation as patients. The contribution of AT2 cell necroptosis to the pathogenesis of pulmonary fibrosis has not been identified in animal model studies, which validates the effectiveness of genetic analysis of familial diseases to uncover unknown pathogeneses. Thus, further extensive genetic studies of pulmonary fibrosis along with functional studies based on genetic analysis will be crucial not only in elucidating the precise disease process but also, ultimately, in identifying novel treatment strategies for both familial and nonfamilial pulmonary fibrosis.

中文翻译：

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家族性肺纤维化的遗传学和动物模型

 抽象的

肺纤维化是由遗传和环境因素相互作用引起的。最近的研究揭示了与特发性肺纤维化相关的多种基因，以及家族性肺纤维化的致病基因。尽管在肺纤维化患者的肺标本中检测到 2 型肺泡上皮 (AT2) 细胞死亡或功能障碍增加，但仍不清楚 AT2 细胞死亡或功能障碍是否以及如何导致肺纤维化进展。最近的一项研究通过分析家族性肺纤维化患者和与患者具有相同突变的动物模型，表明 AT2 细胞坏死性凋亡增加是肺纤维化的初始事件。 AT2细胞坏死性凋亡在肺纤维化发病机制中的作用尚未在动物模型研究中得到证实，这验证了家族性疾病遗传分析揭示未知发病机制的有效性。因此，对肺纤维化进行进一步广泛的遗传学研究以及基于遗传分析的功能研究不仅对于阐明精确的疾病过程至关重要，而且最终对于确定家族性和非家族性肺纤维化的新治疗策略至关重要。