Mossina, A. ; Lukas, C. ; Merl-Pham, J. ; Uhl, F.E.* ; Mutze, K. ; Schamberger, A.C. ; Staab-Weijnitz, C.A. ; Jia, J. ; Yildirim, A.Ö. ; Königshoff, M. ; Hauck, S.M. ; Eickelberg, O. ; Meiners, S.
Cigarette smoke alters the secretome of lung epithelial cells.
Proteomics 17:1600243 (2017)
Cigarette smoke is the most relevant risk factor for the development of lung cancer and chronic obstructive pulmonary disease (COPD). Many of its more than 4500 chemicals are highly reactive thereby altering protein structure and function. Here, we used subcellular fractionation coupled to label-free quantitative mass spectrometry to globally assess alterations in the proteome of different compartments of lung epithelial cells upon exposure to cigarette smoke extract. Proteomic profiling of the human alveolar-derived cell line A549 revealed the most pronounced changes within the cellular secretome with preferential downregulation of proteins involved in wound healing and extracellular matrix (ECM) organization. In particular, secretion of secreted protein acidic and rich in cysteine (SPARC), a matricellular protein that functions in tissue response to injury, was consistently diminished by cigarette smoke extract in various pulmonary epithelial cell lines and primary cells of human and mouse origin as well as in mouse ex vivo lung tissue cultures. Our study reveals a previously unrecognized acute response of lung epithelial cells to cigarette smoke that includes altered secretion of proteins involved in ECM organization and wound healing. This may contribute to sustained alterations in tissue remodeling as observed in lung cancer and COPD.
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Publication type
Article: Journal article
Document type
Scientific Article
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Keywords
Cigarette smoke; Lung; Proteomic profiling; Secretome; Obstructive Pulmonary-disease; Mass-spectrometry; Bronchoalveolar Lavage; Airway Epithelium; Growth-factor; Label-free; Repair; Tissue; Proteome; Sparc
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Publication Year
2017
Prepublished in Year
2016
HGF-reported in Year
2016
ISSN (print) / ISBN
1615-9853
e-ISSN
1615-9861
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Volume: 17,
Issue: 1-2,
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Article Number: 1600243
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Wiley
Publishing Place
Hoboken
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Reviewing status
Peer reviewed
POF-Topic(s)
30202 - Environmental Health
30203 - Molecular Targets and Therapies
80000 - German Center for Lung Research
Research field(s)
Lung Research
Enabling and Novel Technologies
PSP Element(s)
G-501600-004
G-505700-001
G-501600-011
G-501800-801
G-505000-006
G-505000-007
G-501800-802
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Erfassungsdatum
2016-12-14