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Collagen VII is associated with airway remodeling, honeycombing and fibroblast foci in UIP/IPF

Svobodová, Barbora LU ; Löfdahl, Anna LU ; Kadefors, Måns LU ; Ali, Salad Mohamed ; Rosmark, Oskar LU orcid ; Prabhala, Pavan LU ; Magnusson, Mattias LU ; Brunnström, Hans LU orcid ; Lundin, Sofia and Dellgren, Göran , et al. (2025) In American Journal of Pathology
Abstract

Collagen VII is an essential anchoring protein in the basement membrane zone, maintaining the attachment of stratified and pseudostratified epithelia to the underlying interstitial matrix. However, collagen VII is largely unexplored in normal lungs and idiopathic pulmonary fibrosis (IPF), a disease characterized by excessive accumulation of extracellular matrix (ECM) and aberrant re-epithelialization of fibrotic lung parenchyma. Analysis of collagen VII mRNA and protein in IPF distal lungs demonstrated elevated levels compared to normal lungs. To investigate its cellular source and spatial distribution in lung tissue, immunohistochemistry, RNAscope in situ hybridization, and cell culture experiments in combination with analysis of... (More)

Collagen VII is an essential anchoring protein in the basement membrane zone, maintaining the attachment of stratified and pseudostratified epithelia to the underlying interstitial matrix. However, collagen VII is largely unexplored in normal lungs and idiopathic pulmonary fibrosis (IPF), a disease characterized by excessive accumulation of extracellular matrix (ECM) and aberrant re-epithelialization of fibrotic lung parenchyma. Analysis of collagen VII mRNA and protein in IPF distal lungs demonstrated elevated levels compared to normal lungs. To investigate its cellular source and spatial distribution in lung tissue, immunohistochemistry, RNAscope in situ hybridization, and cell culture experiments in combination with analysis of public transcriptomic datasets were performed. In IPF lungs, collagen VII was abundant in pathological remodeled airways and honeycomb cysts, associated with increased basal cell populations. In contrast, in the control lungs, collagen VII was mainly localized in larger airways. RNA sequencing data revealed that epithelial basal cells and KRT5-/KRT17+ aberrant basaloid cells are the primary sources of COL7A1 expression. Furthermore, COL7A1 expression was found in mesenchymal subsets and both collagen VII mRNA and protein were observed in fibroblast foci, another histopathological feature of IPF. In vitro, COL7A1 expression was found to be increased in normal human lung fibroblasts treated with TGF-β1. These findings suggest that collagen VII could be involved in the process of abnormal re-epithelialization in lung fibrosis.

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publication status
epub
subject
in
American Journal of Pathology
publisher
American Society for Investigative Pathology
external identifiers
  • pmid:40311757
ISSN
1525-2191
DOI
10.1016/j.ajpath.2025.03.013
language
English
LU publication?
yes
additional info
Copyright © 2025 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.
id
dd0209b0-f72e-4bea-8f86-720909818dd6
date added to LUP
2025-05-04 12:29:09
date last changed
2025-05-05 08:12:13
@article{dd0209b0-f72e-4bea-8f86-720909818dd6,
  abstract     = {{<p>Collagen VII is an essential anchoring protein in the basement membrane zone, maintaining the attachment of stratified and pseudostratified epithelia to the underlying interstitial matrix. However, collagen VII is largely unexplored in normal lungs and idiopathic pulmonary fibrosis (IPF), a disease characterized by excessive accumulation of extracellular matrix (ECM) and aberrant re-epithelialization of fibrotic lung parenchyma. Analysis of collagen VII mRNA and protein in IPF distal lungs demonstrated elevated levels compared to normal lungs. To investigate its cellular source and spatial distribution in lung tissue, immunohistochemistry, RNAscope in situ hybridization, and cell culture experiments in combination with analysis of public transcriptomic datasets were performed. In IPF lungs, collagen VII was abundant in pathological remodeled airways and honeycomb cysts, associated with increased basal cell populations. In contrast, in the control lungs, collagen VII was mainly localized in larger airways. RNA sequencing data revealed that epithelial basal cells and KRT5-/KRT17+ aberrant basaloid cells are the primary sources of COL7A1 expression. Furthermore, COL7A1 expression was found in mesenchymal subsets and both collagen VII mRNA and protein were observed in fibroblast foci, another histopathological feature of IPF. In vitro, COL7A1 expression was found to be increased in normal human lung fibroblasts treated with TGF-β1. These findings suggest that collagen VII could be involved in the process of abnormal re-epithelialization in lung fibrosis.</p>}},
  author       = {{Svobodová, Barbora and Löfdahl, Anna and Kadefors, Måns and Ali, Salad Mohamed and Rosmark, Oskar and Prabhala, Pavan and Magnusson, Mattias and Brunnström, Hans and Lundin, Sofia and Dellgren, Göran and Müller, Catharina and Elowsson, Linda and Westergren-Thorsson, Gunilla}},
  issn         = {{1525-2191}},
  language     = {{eng}},
  month        = {{04}},
  publisher    = {{American Society for Investigative Pathology}},
  series       = {{American Journal of Pathology}},
  title        = {{Collagen VII is associated with airway remodeling, honeycombing and fibroblast foci in UIP/IPF}},
  url          = {{http://dx.doi.org/10.1016/j.ajpath.2025.03.013}},
  doi          = {{10.1016/j.ajpath.2025.03.013}},
  year         = {{2025}},
}