Time‐ and compartment‐resolved proteome profiling of the extracellular niche in lung injury and repair

• Published in: Molecular systems biology Vol. 11; no. 7; pp. 819 - n/a
• Main Authors: Schiller, Herbert B, Fernandez, Isis E, Burgstaller, Gerald, Schaab, Christoph, Scheltema, Richard A, Schwarzmayr, Thomas, Strom, Tim M, Eickelberg, Oliver, Mann, Matthias
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.07.2015; EMBO Press; John Wiley & Sons, Ltd; Springer Nature
• Subjects: Alveoli; Animals; Bleomycin; Bleomycin - toxicity; Bronchoalveolar Lavage Fluid; Bronchus; Collagen; Collagen - metabolism; Composition; Datasets; Disease Models, Animal; EMBO17; EMBO24; EMBO31; Experiments; Extracellular matrix; Extracellular Matrix - metabolism; Female; Fibrosis; Gene expression; Gene Expression Regulation; Glycoproteins - metabolism; Injuries; Lung - metabolism; Lung - physiopathology; Lung diseases; Lung Injury - chemically induced; Lung Injury - metabolism; Lung Injury - pathology; Lungs; Mass spectrometry; Mass spectroscopy; Mice; Morphogenesis; Peptides; Physiology; Principal components analysis; Proteins; Proteomes; Proteomics; Proteomics - methods; Pulmonary fibrosis; regeneration; Repair; Respiratory tract; Scientific imaging; Secretome; Signal transduction; Software; Surveying; Tissues; Transcription; fibrosis; proteomics; secretome; regeneration; extracellular matrix
• ISSN: 1744-4292; 1744-4292
• DOI: 10.15252/msb.20156123

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. Synopsis A proteome‐wide view of lung injury and repair was elucidated by mass spectrometry analysis of the dynamic composition of lung tissue compartments. In particular, the extracellular matrix proteome uncovers potential factors in stem cell mobilization and fibrosis resolution. Proteomic analysis discovers signatures of consecutive phases of lung injury, fibrosis, and repair. Combined proteomics and transcriptomics define the prevalence of post‐transcriptional events. Compartment proteomics uncovers extracellular matrix and epithelial lining fluid composition. In vivo solubility profiling reveals extracellular matrix interactions with secreted proteins. Graphical Abstract A proteome‐wide view of lung injury and repair was elucidated by mass spectrometry analysis of the dynamic composition of lung tissue compartments. In particular, the extracellular matrix proteome uncovers potential factors in stem cell mobilization and fibrosis resolution.