CD248 and integrin alpha-8 are candidate markers for differentiating lung fibroblast subtypes
CD248 and integrin alpha-8 are candidate markers for differentiating lung fibroblast subtypes
复制标题
DOI：
10.1186/s12890-020-1054-9
复制
发表时间：
2020-01-21
影响因子：
3.1
通讯作者：
Iwashita, Toshihide
中科院分区：
文献类型：
--
作者：
Matsushima, Sayomi;Aoshima, Yoichiro;Iwashita, Toshihide
肺纤维化是一种严重危及生命的疾病，其表现因成纤维细胞的定位和特征而异，成纤维细胞被认为是异质的。因此，为了更好地了解该病的病理，提高该病的诊断和治疗水平，有必要阐明这种异质性的本质，并确定准确分类人肺成纤维细胞亚型的标记物。方法采用荧光活化细胞分选（FACS）技术对不同的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。基于这些标记的表达，我们评估了正常人类肺样本和特发性肺纤维化（IPF）患者肺样本中成纤维细胞样细胞亚型定位。结果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CD248和整合素α -8 （ITGA8）分别是Sca-1（高）成纤维细胞和Sca-1（低）成纤维细胞的细胞表面标记物。在小鼠肺中，Sca-1（高含量）成纤维细胞和Sca-1（低含量）成纤维细胞分别定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。在正常人和IPF肺中，鉴定出两种相应的主要成纤维细胞样细胞亚型：CD248（高）ITGA8（低）成纤维细胞样细胞和CD248（低）ITGA8（高）成纤维细胞样细胞，分别定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。结论CD248（高）ITGA8（低）成纤维细胞样细胞和CD248（低）ITGA8（高）成纤维细胞样细胞在人肺标本中几乎排他定位。利用两种细胞表面标记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，从而为肺发育和纤维化性肺疾病的病理过程提供新的见解。
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-1(high) fibroblasts and Sca-1(low) fibroblasts by in vitro biological analyses. Through microarray analysis, we demonstrated CD248 and integrin alpha-8 (ITGA8) as cell surface markers for Sca-1(high) fibroblasts and Sca-1(low) fibroblasts, respectively. In mouse lungs, Sca-1(high) fibroblasts and Sca-1(low) 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: CD248(high)ITGA8(low) fibroblast-like cells and CD248(low)ITGA8(high) fibroblast-like cells, localized in the collagen fiber-rich connective tissue and in the elastic fiber-rich connective tissue, respectively. Conclusion CD248(high)ITGA8(low) fibroblast-like cells and CD248(low)ITGA8(high) 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.