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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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Figure 1

The myofibroblast core of the fibroblastic focus is defined by collagen I and cells expressing α-smooth muscle actin and procollagen I.

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The myofibroblast core of the fibroblastic focus is defined by collagen ...
(A and B) Twelve IPF specimens were assembled into a tissue microarray, serially sectioned at 5 μm, and immunostained for collagen I (left), α-smooth muscle actin (αSMA; middle), and procollagen I (right). (A) Low-magnification images of 2 IPF specimen serial section core punches. Red arrows show regions of high collagen I deposition traced through the serial stains. Scale bar: 500 μm. (B) High-magnification images of 3 IPF specimens. The myofibroblast core of the fibroblastic focus is outlined by red dotted lines. Scale bar: 100 μm. (C) The myofibroblast core of the fibroblastic focus, characterized by collagen I immunoreactivity, was scored as either positive (score = 1) or negative (score = 0) immunoreactivity for αSMA or procollagen I. Each myofibroblast core was serially immunostained up to 4 times for αSMA and procollagen I, and their averaged score is represented as a single data point on the graph. A χ2 test was performed for αSMA and procollagen I association with collagen I; P = 0.9999 for both (n = 29 fibroblastic foci for αSMA, n = 29 fibroblastic foci for procollagen I; n = 12 IPF patients total [1–6 fibroblastic foci per patient]).

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