Time- and compartment-resolved proteome profiling of the extracellular niche in lung injury and repair
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The extracellular matrix (ECM) is a key regulator of tissue morphogenesis and repair. However, its composition and architecture are not well characterized. Here, we monitor remodeling of the extracellular niche in tissue repair in the bleomycin-induced lung injury mouse model. Mass spectrometry quantified 8,366 proteins from total tissue and bronchoalveolar lavage fluid (BALF) over the course of 8 weeks, surveying tissue composition from the onset of inflammation and fibrosis to its full recovery. Combined analysis of proteome, secretome, and transcriptome highlighted post-transcriptional events during tissue fibrogenesis and defined the composition of airway epithelial lining fluid. To comprehensively characterize the ECM, we developed a quantitative detergent solubility profiling (QDSP) method, which identified Emilin-2 and collagen-XXVIII as novel constituents of the provisional repair matrix. QDSP revealed which secreted proteins interact with the ECM, and showed drastically altered association of morphogens to the insoluble matrix upon injury. Thus, our proteomic systems biology study assigns proteins to tissue compartments and uncovers their dynamic regulation upon lung injury and repair, potentially contributing to the development of anti-fibrotic strategies.
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Gene expression analysis has proven inadequate to fully describe the proteome, including the tissue matrix environment.
“However, gene expression analysis has proven inadequate to fully describe the proteome, including the tissue matrix environment”
From Defining the Adult Neural Stem Cell Niche Proteome Identifies Key Regulators of Adult Neurogenesis (2020) · cites this paper as Schiller et al., 2015
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Godin, L. M., Sandri, B. J., Wagner, D. E., Meyer, C. M., Price, A. P., Akinnola, I., Weiss, D. J., & Panoskaltsis-Mortari, A. (2016) · PLOS ONE · doi:10.1371/journal.pone.0150966 · Cited by 68 · see citing works
Regeneration and repair in the healing lung
Lucas, A., Yasa, J., & Lucas, M. (2020) · Clinical & Translational Immunology · doi:10.1002/cti2.1152 · Cited by 41 · see citing works
- Authors
- Schiller, H. B., Fernandez, I. E., Burgstaller, G., Schaab, C., Scheltema, R. A., Schwarzmayr, T., Strom, T. M., Eickelberg, O., & Mann, M.
- Affiliations
- Max Planck Institute of Biochemistry (DE)
- Helmholtz Munich (DE)
- Corresponding author
- Schiller, Herbert B
- Eickelberg, Oliver
- Mann, Matthias
- ORCID
- Venue
- Molecular Systems Biology
- Published
- 2015-07-01
- Volume
- 11
- Issue
- 7
- Pages
- 819-819
- ISSN
- 1744-4292 (ISSN-L)
- PMC
- PMC4547847
- OpenAlex
- W2104947426
- Cited by
- 261
- References
- 81
- Citations by year
- 2026: 11 · 2025: 29 · 2024: 28 · 2023: 30 · 2022: 22 · 2021: 36 · 2020: 35 · 2019: 20 · 2018: 20 · 2017: 17 · 2016: 10 · 2015: 3
- FWCI
- 13.20
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Molecular Systems Biology (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- PuSH - Publication Server of Helmholtz Zentrum München (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Open access LMU (Ludwid Maxmilian's Universitat Munchen) (submittedVersion)
- Site cant be reached (submittedVersion, cc-by)
- MPG.PuRe (Max Planck Society) (submittedVersion, other-oa)
- Funders
- Max‐Planck Society for the Advancement of Science
- German Center of Lung Research
- Helmholtz Association
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
- Physical Sciences › Chemistry › Spectroscopy › Mass Spectrometry Techniques and Applications
- Keywords
- lung injury, lung repair, extracellular matrix, bleomycin-induced lung fibrosis, bronchoalveolar lavage fluid, secretome, proteomic profiling, morphogens, post-transcriptional regulation
- MeSH terms
- Animals, Bleomycin, Bronchoalveolar Lavage Fluid, Collagen, Disease Models, Animal, Extracellular Matrix, Female, Gene Expression Regulation, Glycoproteins, Lung, Proteomics, Mice, Lung Injury
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