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Distal lung microenvironment triggers release of mediators recognized as potential systemic biomarkers for idiopathic pulmonary fibrosis

Kalafatis, Dimitrios ; Löfdahl, Anna LU ; Näsman, Per ; Dellgren, Göran ; Wheelock, Åsa M. ; Rendin, Linda Elowsson LU ; Sköld, Magnus and Westergren-Thorsson, Gunilla LU (2021) In International Journal of Molecular Sciences 22(24).
Abstract

Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease with an unmet need of biomarkers that can aid in the diagnostic and prognostic assessment of the disease and response to treatment. In this two-part explorative proteomic study, we demonstrate how proteins associated with tissue remodeling, inflammation and chemotaxis such as MMP7, CXCL13 and CCL19 are released in response to aberrant extracellular matrix (ECM) in IPF lung. We used a novel ex vivo model where decellularized lung tissue from IPF patients and healthy donors were repopulated with healthy fibroblasts to monitor locally released mediators. Results were validated in longitudinally collected serum samples from 38 IPF patients and from 77 healthy... (More)

Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease with an unmet need of biomarkers that can aid in the diagnostic and prognostic assessment of the disease and response to treatment. In this two-part explorative proteomic study, we demonstrate how proteins associated with tissue remodeling, inflammation and chemotaxis such as MMP7, CXCL13 and CCL19 are released in response to aberrant extracellular matrix (ECM) in IPF lung. We used a novel ex vivo model where decellularized lung tissue from IPF patients and healthy donors were repopulated with healthy fibroblasts to monitor locally released mediators. Results were validated in longitudinally collected serum samples from 38 IPF patients and from 77 healthy controls. We demonstrate how proteins elevated in the ex vivo model (e.g., MMP7), and other serum proteins found elevated in IPF patients such as HGF, VEGFA, MCP-3, IL-6 and TNFRSF12A, are associated with disease severity and progression and their response to antifibrotic treatment. Our study supports the model’s applicability in studying mechanisms involved in IPF and provides additional evidence for both established and potentially new biomarkers in IPF.

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author
; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Biomarkers, Extracellular matrix, Fibroblast, Idiopathic pulmonary fibrosis
in
International Journal of Molecular Sciences
volume
22
issue
24
article number
13421
publisher
MDPI AG
external identifiers
  • scopus:85121343122
  • pmid:34948231
ISSN
1661-6596
DOI
10.3390/ijms222413421
language
English
LU publication?
yes
id
6d4eb194-b010-4a77-acf7-1c1404a54769
date added to LUP
2022-01-26 17:16:20
date last changed
2022-09-25 03:08:55
@article{6d4eb194-b010-4a77-acf7-1c1404a54769,
  abstract     = {{<p>Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease with an unmet need of biomarkers that can aid in the diagnostic and prognostic assessment of the disease and response to treatment. In this two-part explorative proteomic study, we demonstrate how proteins associated with tissue remodeling, inflammation and chemotaxis such as MMP7, CXCL13 and CCL19 are released in response to aberrant extracellular matrix (ECM) in IPF lung. We used a novel ex vivo model where decellularized lung tissue from IPF patients and healthy donors were repopulated with healthy fibroblasts to monitor locally released mediators. Results were validated in longitudinally collected serum samples from 38 IPF patients and from 77 healthy controls. We demonstrate how proteins elevated in the ex vivo model (e.g., MMP7), and other serum proteins found elevated in IPF patients such as HGF, VEGFA, MCP-3, IL-6 and TNFRSF12A, are associated with disease severity and progression and their response to antifibrotic treatment. Our study supports the model’s applicability in studying mechanisms involved in IPF and provides additional evidence for both established and potentially new biomarkers in IPF.</p>}},
  author       = {{Kalafatis, Dimitrios and Löfdahl, Anna and Näsman, Per and Dellgren, Göran and Wheelock, Åsa M. and Rendin, Linda Elowsson and Sköld, Magnus and Westergren-Thorsson, Gunilla}},
  issn         = {{1661-6596}},
  keywords     = {{Biomarkers; Extracellular matrix; Fibroblast; Idiopathic pulmonary fibrosis}},
  language     = {{eng}},
  number       = {{24}},
  publisher    = {{MDPI AG}},
  series       = {{International Journal of Molecular Sciences}},
  title        = {{Distal lung microenvironment triggers release of mediators recognized as potential systemic biomarkers for idiopathic pulmonary fibrosis}},
  url          = {{http://dx.doi.org/10.3390/ijms222413421}},
  doi          = {{10.3390/ijms222413421}},
  volume       = {{22}},
  year         = {{2021}},
}