Herrera Jeremy, Forster Colleen, Pengo Thomas, Montero Angeles, Swift Joe, Schwartz Martin A, Henke Craig A, Bitterman Peter B
Wellcome Centre for Cell-Matrix Research, Manchester Academic Health Science Centre, University of Manchester, Manchester, United Kingdom.
University of Minnesota, Clinical and Translational Science Institute, Minneapolis, Minnesota, USA.
JCI Insight. 2019 Jan 10;4(1):e125185. doi: 10.1172/jci.insight.125185.
The extracellular matrix (ECM) in idiopathic pulmonary fibrosis (IPF) drives fibrosis progression; however, the ECM composition of the fibroblastic focus (the hallmark lesion in IPF) and adjacent regions remains incompletely defined. Herein, we serially sectioned IPF lung specimens constructed into tissue microarrays and immunostained for ECM components reported to be deregulated in IPF. Immunostained sections were imaged, anatomically aligned, and 3D reconstructed. The myofibroblast core of the fibroblastic focus (defined by collagen I, α-smooth muscle actin, and procollagen I immunoreactivity) was associated with collagens III, IV, V, and VI; fibronectin; hyaluronan; and versican immunoreactivity. Hyaluronan immunoreactivity was also present at the fibroblastic focus perimeter and at sites where early lesions appear to be forming. Fibrinogen immunoreactivity was often observed at regions of damaged epithelium lining the airspace and the perimeter of the myofibroblast core but was absent from the myofibroblast core itself. The ECM components of the fibroblastic focus were distributed in a characteristic and reproducible manner in multiple patients. This information can inform the development of high-fidelity model systems to dissect mechanisms by which the IPF ECM drives fibrosis progression.
特发性肺纤维化（IPF）中的细胞外基质（ECM）推动纤维化进展；然而，成纤维细胞灶（IPF中的标志性病变）及其相邻区域的ECM组成仍未完全明确。在此，我们对构建成组织微阵列的IPF肺标本进行连续切片，并对据报道在IPF中失调的ECM成分进行免疫染色。对免疫染色的切片进行成像、解剖学对齐和三维重建。成纤维细胞灶的肌成纤维细胞核心（由I型胶原蛋白、α平滑肌肌动蛋白和前胶原蛋白I免疫反应性定义）与III型、IV型、V型和VI型胶原蛋白；纤连蛋白；透明质酸；和多功能蛋白聚糖免疫反应性相关。透明质酸免疫反应性也出现在成纤维细胞灶周边以及早期病变似乎正在形成的部位。纤维蛋白原免疫反应性经常在气腔衬里受损上皮区域和成纤维细胞核心周边观察到，但在成纤维细胞核心本身不存在。成纤维细胞灶的ECM成分在多名患者中以特征性且可重复的方式分布。这些信息可为开发高保真模型系统提供依据，以剖析IPF ECM驱动纤维化进展的机制。
