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Registration of the extracellular matrix components constituting the fibroblastic focus in idiopathic pulmonary fibrosis
Jeremy Herrera, … , Craig A. Henke, Peter B. Bitterman
Jeremy Herrera, … , Craig A. Henke, Peter B. Bitterman
Published January 10, 2019
Citation Information: JCI Insight. 2019;4(1):e125185. https://doi.org/10.1172/jci.insight.125185.
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Research Article Pulmonology

Registration of the extracellular matrix components constituting the fibroblastic focus in idiopathic pulmonary fibrosis

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Abstract

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.

Authors

Jeremy Herrera, Colleen Forster, Thomas Pengo, Angeles Montero, Joe Swift, Martin A. Schwartz, Craig A. Henke, Peter B. Bitterman

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