Registration of the extracellular matrix components constituting the fibroblastic focus in idiopathic pulmonary fibrosis
Registration of the extracellular matrix components constituting the fibroblastic focus in idiopathic pulmonary fibrosis
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DOI：
10.1172/jci.insight.125185
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发表时间：
2019-01-10
期刊：
影响因子：
8
通讯作者：
Bitterman, Peter B.
中科院分区：
文献类型：
--
作者：
Herrera, Jeremy;Forster, Colleen;Bitterman, Peter B.
特发性肺纤维化 (IPF) 中的细胞外基质 (ECM) 驱动纤维化进展；然而，成纤维细胞灶（IPF 的标志性病变）和邻近区域的 ECM 组成仍未完全确定。在此，我们对 IPF 肺标本进行连续切片，构建成组织微阵列，并对据报告在 IPF 中失调的 ECM 成分进行免疫染色。对免疫染色切片进行成像、解剖学对齐和 3D 重建。成纤维细胞灶的肌成纤维细胞核心（由 I 型胶原、α-平滑肌肌动蛋白和 I 型前胶原免疫反应性定义）与 III、IV、V 和 VI 型胶原相关；纤连蛋白；透明质酸；和多功能免疫反应性。透明质酸免疫反应性也存在于成纤维细胞病灶周边和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衬在空腔和肌成纤维细胞核心周边的受损上皮区域观察到，但肌成纤维细胞核心本身不存在。成纤维细胞病灶的 ECM 成分在多个患者中以特征性且可重复的方式分布。这些信息可以为高保真模型系统的开发提供信息，以剖析 IPF ECM 驱动纤维化进展的机制。
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, alpha-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.