Quantitative proteomic characterization of the lung extracellular matrix in chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis
Åhrman, Emma LU ; Hallgren, Oskar LU ; Malmström, Lars LU ; Hedström, Ulf LU ; Malmström, Anders LU
; Bjermer, Leif
LU
; Zhou, Xiao Hong
; Westergren-Thorsson, Gunilla
LU
and Malmström, Johan
LU
(2018)
In Journal of Proteomics
189.
p.23-33
- Abstract
Remodeling of the extracellular matrix (ECM) is a common feature in lung diseases such as chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF). Here, we applied a sequential tissue extraction strategy to describe disease-specific remodeling of human lung tissue in disease, using end-stages of COPD and IPF. Our strategy was based on quantitative comparison of the disease proteomes, with specific focus on the matrisome, using data-independent acquisition and targeted data analysis (SWATH-MS). Our work provides an in-depth proteomic characterization of human lung tissue during impaired tissue remodeling. In addition, we show important quantitative and qualitative effects of the solubility of matrisome... (More)
Remodeling of the extracellular matrix (ECM) is a common feature in lung diseases such as chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF). Here, we applied a sequential tissue extraction strategy to describe disease-specific remodeling of human lung tissue in disease, using end-stages of COPD and IPF. Our strategy was based on quantitative comparison of the disease proteomes, with specific focus on the matrisome, using data-independent acquisition and targeted data analysis (SWATH-MS). Our work provides an in-depth proteomic characterization of human lung tissue during impaired tissue remodeling. In addition, we show important quantitative and qualitative effects of the solubility of matrisome proteins. COPD was characterized by a disease-specific increase in ECM regulators, metalloproteinase inhibitor 3 (TIMP3) and matrix metalloproteinase 28 (MMP-28), whereas for IPF, impairment in cell adhesion proteins, such as collagen VI and laminins, was most prominent. For both diseases, we identified increased levels of proteins involved in the regulation of endopeptidase activity, with several proteins belonging to the serpin family. The established human lung quantitative proteome inventory and the construction of a tissue-specific protein assay library provides a resource for future quantitative proteomic analyses of human lung tissues. Significance: We present a sequential tissue extraction strategy to determine changes in extractability of matrisome proteins in end-stage COPD and IPF compared to healthy control tissue. Extensive quantitative analysis of the proteome changes of the disease states revealed altered solubility of matrisome proteins involved in ECM regulators and cell-ECM communication. The results highlight disease-specific remodeling mechanisms associated with COPD and IPF.
(Less)
- author
- Åhrman, Emma
LU
; Hallgren, Oskar
LU
; Malmström, Lars
LU
; Hedström, Ulf
LU
; Malmström, Anders
LU
; Bjermer, Leif
LU
; Zhou, Xiao Hong
; Westergren-Thorsson, Gunilla
LU
and Malmström, Johan
LU
- organization
- publishing date
- 2018-03-01
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- COPD, IPF, Lung tissue, Matrisome, Quantitative proteomics, SWATH-MS
- in
- Journal of Proteomics
- volume
- 189
- pages
- 23 - 33
- publisher
- Elsevier
- external identifiers
-
- scopus:85043352705
- pmid:29501846
- ISSN
- 1874-3919
- DOI
- 10.1016/j.jprot.2018.02.027
- language
- English
- LU publication?
- yes
- id
- 8de3b2a1-8410-4f38-8e53-97a2cc8933d5
- date added to LUP
- 2018-03-22 12:58:09
- date last changed
- 2024-04-01 01:22:16
@article{8de3b2a1-8410-4f38-8e53-97a2cc8933d5,
abstract = {{<p>Remodeling of the extracellular matrix (ECM) is a common feature in lung diseases such as chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF). Here, we applied a sequential tissue extraction strategy to describe disease-specific remodeling of human lung tissue in disease, using end-stages of COPD and IPF. Our strategy was based on quantitative comparison of the disease proteomes, with specific focus on the matrisome, using data-independent acquisition and targeted data analysis (SWATH-MS). Our work provides an in-depth proteomic characterization of human lung tissue during impaired tissue remodeling. In addition, we show important quantitative and qualitative effects of the solubility of matrisome proteins. COPD was characterized by a disease-specific increase in ECM regulators, metalloproteinase inhibitor 3 (TIMP3) and matrix metalloproteinase 28 (MMP-28), whereas for IPF, impairment in cell adhesion proteins, such as collagen VI and laminins, was most prominent. For both diseases, we identified increased levels of proteins involved in the regulation of endopeptidase activity, with several proteins belonging to the serpin family. The established human lung quantitative proteome inventory and the construction of a tissue-specific protein assay library provides a resource for future quantitative proteomic analyses of human lung tissues. Significance: We present a sequential tissue extraction strategy to determine changes in extractability of matrisome proteins in end-stage COPD and IPF compared to healthy control tissue. Extensive quantitative analysis of the proteome changes of the disease states revealed altered solubility of matrisome proteins involved in ECM regulators and cell-ECM communication. The results highlight disease-specific remodeling mechanisms associated with COPD and IPF.</p>}},
author = {{Åhrman, Emma and Hallgren, Oskar and Malmström, Lars and Hedström, Ulf and Malmström, Anders and Bjermer, Leif and Zhou, Xiao Hong and Westergren-Thorsson, Gunilla and Malmström, Johan}},
issn = {{1874-3919}},
keywords = {{COPD; IPF; Lung tissue; Matrisome; Quantitative proteomics; SWATH-MS}},
language = {{eng}},
month = {{03}},
pages = {{23--33}},
publisher = {{Elsevier}},
series = {{Journal of Proteomics}},
title = {{Quantitative proteomic characterization of the lung extracellular matrix in chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis}},
url = {{http://dx.doi.org/10.1016/j.jprot.2018.02.027}},
doi = {{10.1016/j.jprot.2018.02.027}},
volume = {{189}},
year = {{2018}},
}