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08 22, 2022;7 (16):

The UIP/IPF fibroblastic focus is a collagen biosynthesis factory embedded in a distinct extracellular matrix.

Jeremy A Herrera, Lewis Dingle, M Angeles Montero, Rajamiyer V Venkateswaran, John F Blaikley, Craig Lawless, Martin A Schwartz
Author Information
  1. Jeremy A Herrera: The Wellcome Centre for Cell-Matrix Research and.
  2. Lewis Dingle: Blond McIndoe Laboratories, University of Manchester, Manchester Academic Health Science Centre, Manchester, United Kingdom.
  3. M Angeles Montero: Department of Histopathology, Manchester University National Health Service Foundation Trust, Manchester, United Kingdom.
  4. Rajamiyer V Venkateswaran: Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, United Kingdom.
  5. John F Blaikley: Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, United Kingdom.
  6. Craig Lawless: The Wellcome Centre for Cell-Matrix Research and.
  7. Martin A Schwartz: The Wellcome Centre for Cell-Matrix Research and.
PMID: 35852874 DOI: 10.1172/jci.insight.156115

Abstract

Usual interstitial pneumonia (UIP) is a histological pattern characteristic of idiopathic pulmonary fibrosis (IPF). The UIP pattern is patchy with histologically normal lung adjacent to dense fibrotic tissue. At this interface, fibroblastic foci (FF) are present and are sites where myofibroblasts and extracellular matrix (ECM) accumulate. Utilizing laser capture microdissection-coupled mass spectrometry, we interrogated the FF, adjacent mature scar, and adjacent alveoli in 6 fibrotic (UIP/IPF) specimens plus 6 nonfibrotic alveolar specimens as controls. The data were subjected to qualitative and quantitative analysis and histologically validated. We found that the fibrotic alveoli protein signature is defined by immune deregulation as the strongest category. The fibrotic mature scar classified as end-stage fibrosis whereas the FF contained an overabundance of a distinctive ECM compared with the nonfibrotic control. Furthermore, FF were positive for both TGFB1 and TGFB3, whereas the aberrant basaloid cell lining of FF was predominantly positive for TGFB2. In conclusion, spatial proteomics demonstrated distinct protein compositions in the histologically defined regions of UIP/IPF tissue. These data revealed that FF are the main site of collagen biosynthesis and that the adjacent alveoli are abnormal. This essential information will inform future mechanistic studies on fibrosis progression.

Keywords

Extracellular matrix Fibrosis Proteomics Pulmonology

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Grants

  1. /Wellcome Trust
  2. MR/T032529/1/Medical Research Council
  3. R01 HL135582/NHLBI NIH HHS

MeSH Term

Cicatrix
Collagen
Extracellular Matrix
Fibrosis
Humans
Idiopathic Pulmonary Fibrosis

Chemicals

Collagen
Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't
Article has an altmetric score of 4

Word Cloud

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