Open AccessTime‐ and compartment‐resolved proteome profiling of the extracellular niche in lung injury and repair
Author(s) -
Schiller Herbert B,
Fernandez Isis E,
Burgstaller Gerald,
Schaab Christoph,
Scheltema Richard A,
Schwarzmayr Thomas,
Strom Tim M,
Eickelberg Oliver,
Mann Matthias
Publication year - 2015
Publication title -
molecular systems biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 8.523
H-Index - 148
ISSN - 1744-4292
DOI - 10.15252/msb.20156123
Subject(s) - extracellular matrix , biology , proteome , microbiology and biotechnology , bronchoalveolar lavage , fibrosis , transcriptome , myofibroblast , lung , pathology , bioinformatics , biochemistry , gene expression , gene , medicine , linguistics , philosophy
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.