title: Time- and compartment-resolved proteome profiling of the extracellular niche in lung injury and repair.
abstract: 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.
authors.affiliation: Department of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Martinsried, Germany hschille@biochem.mpg.de oliver.eickelberg@helmholtz-muenchen.de mmann@biochem.mpg.de.
authors.forename: Herbert B
authors.initials: HB
authors.lastname: Schiller
authors.affiliation: Comprehensive Pneumology Center, University Hospital of the Ludwig-Maximilians-University Munich and Helmholtz Zentrum München, Member of the German Center for Lung Research (DZL), Munich, Germany.
authors.forename: Isis E
authors.initials: IE
authors.lastname: Fernandez
authors.affiliation: Comprehensive Pneumology Center, University Hospital of the Ludwig-Maximilians-University Munich and Helmholtz Zentrum München, Member of the German Center for Lung Research (DZL), Munich, Germany.
authors.forename: Gerald
authors.initials: G
authors.lastname: Burgstaller
authors.affiliation: Department of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Martinsried, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Schaab
authors.affiliation: Department of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Martinsried, Germany.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Scheltema
authors.affiliation: Institute of Human Genetics, Helmholtz Zentrum München, Neuherberg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Schwarzmayr
authors.affiliation: Institute of Human Genetics, Helmholtz Zentrum München, Neuherberg, Germany.
authors.forename: Tim M
authors.initials: TM
authors.lastname: Strom
authors.affiliation: Comprehensive Pneumology Center, University Hospital of the Ludwig-Maximilians-University Munich and Helmholtz Zentrum München, Member of the German Center for Lung Research (DZL), Munich, Germany hschille@biochem.mpg.de oliver.eickelberg@helmholtz-muenchen.de mmann@biochem.mpg.de.
authors.forename: Oliver
authors.initials: O
authors.lastname: Eickelberg
authors.affiliation: Department of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Martinsried, Germany hschille@biochem.mpg.de oliver.eickelberg@helmholtz-muenchen.de mmann@biochem.mpg.de.
authors.forename: Matthias
authors.initials: M
authors.lastname: Mann
mesh_terms: D000818:Animals; D001761:Bleomycin / Q000633:toxicity; D001992:Bronchoalveolar Lavage Fluid; D003094:Collagen / Q000378:metabolism; D004195:Disease Models, Animal; D005109:Extracellular Matrix / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D006023:Glycoproteins / Q000378:metabolism; D008168:Lung / Q000378:metabolism / Q000503:physiopathology; D055370:Lung Injury / Q000139:chemically induced* / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D040901:Proteomics / Q000379:methods*
chemical_list: C426245:EMILIN2 protein, human; D006023:Glycoproteins; D001761:Bleomycin; D003094:Collagen
keywords: extracellular matrix; fibrosis; proteomics; regeneration; secretome