BACKGROUND Lung fibrosis is a serious life-threatening condition whose manifestation varies according to the localization and characteristics of fibroblasts, which are considered heterogeneous. Therefore, to better understand the pathology and improve diagnosis and treatment of this disease, it is necessary to elucidate the nature of this heterogeneity and identify markers for the accurate classification of human lung fibroblast subtypes. METHODS We characterized distinct mouse lung fibroblast subpopulations isolated by fluorescence-activated cell sorting (FACS) and performed microarray analysis to identify molecular markers that could be useful for human lung fibroblast classification. Based on the expression of these markers, we evaluated the fibroblast-like cell subtype localization in normal human lung samples and lung samples from patients with idiopathic pulmonary fibrosis (IPF). RESULTS Mouse lung fibroblasts were classified into Sca-1high fibroblasts and Sca-1low fibroblasts by in vitro biological analyses. Through microarray analysis, we demonstrated CD248 and integrin alpha-8 (ITGA8) as cell surface markers for Sca-1high fibroblasts and Sca-1low fibroblasts, respectively. In mouse lungs, Sca-1high fibroblasts and Sca-1low fibroblasts were localized in the collagen fiber-rich connective tissue and elastic fiber-rich connective tissue, respectively. In normal human lungs and IPF lungs, two corresponding major fibroblast-like cell subtypes were identified: CD248highITGA8low fibroblast-like cells and CD248lowITGA8high fibroblast-like cells, localized in the collagen fiber-rich connective tissue and in the elastic fiber-rich connective tissue, respectively. CONCLUSION CD248highITGA8low fibroblast-like cells and CD248lowITGA8high fibroblast-like cells were localized in an almost exclusive manner in human lung specimens. This human lung fibroblast classification using two cell surface markers may be helpful for further detailed investigations of the functions of lung fibroblast subtypes, which can provide new insights into lung development and the pathological processes underlying fibrotic lung diseases.

中文翻译：

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CD248和整联蛋白alpha-8是区分肺成纤维细胞亚型的候选标记。

背景技术肺纤维化是一种严重的威胁生命的疾病，其表现根据成纤维细胞的定位和特征而异，被认为是异质的。因此，为了更好地了解这种疾病的病理学并改善其诊断和治疗，有必要阐明这种异质性的性质，并确定用于准确分类人肺成纤维细胞亚型的标志物。方法我们对通过荧光激活细胞分选（FACS）分离的不同小鼠肺成纤维细胞亚群进行了表征，并进行了微阵列分析，以鉴定可用于人肺成纤维细胞分类的分子标记。根据这些标记的表达，我们评估了正常人肺样品和特发性肺纤维化（IPF）患者肺样品中的成纤维样细胞亚型定位。结果通过体外生物学分析，将小鼠肺成纤维细胞分为Sca-1高成纤维细胞和Sca-1低成纤维细胞。通过微阵列分析，我们证明了CD248和整联蛋白α-8（ITGA8）分别作为Sca-1高成纤维细胞和Sca-1低成纤维细胞的细胞表面标记。在小鼠肺中，Sca-1高成纤维细胞和Sca-1低成纤维细胞分别位于富含胶原纤维的结缔组织和富含弹性纤维的结缔组织中。在正常人肺和IPF肺中，鉴定出两种相应的主要成纤维细胞样细胞亚型：CD248highITGA8low成纤维细胞样细胞和CD248lowITGA8high成纤维细胞样细胞，分别位于富含胶原纤维的结缔组织和富含弹性纤维的结缔组织中。结论CD248highITGA8low成纤维细胞样细胞和CD248lowITGA8high成纤维细胞样细胞以几乎排他的方式定位于人肺标本中。使用两种细胞表面标志物对人肺成纤维细胞进行分类可能有助于进一步详细研究肺成纤维细胞亚型的功能，这可以为肺发育和纤维化性肺部疾病的病理过程提供新的见解。