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Schiller, H. B.* ; Fernandez, I.E. ; Burgstaller, G. ; Schaab, C.* ; Scheltema, R.A.* ; Schwarzmayr, T. ; Strom, T.M. ; Eickelberg, O. ; Mann, M.*

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

Mol. Syst. Biol. 11:819 (2015)
Verlagsversion DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
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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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Extracellular Matrix ; Fibrosis ; Proteomics ; Regeneration ; Secretome; Idiopathic Pulmonary-fibrosis; Airway Stem-cells; Branching-morphogenesis; Endothelial-cells; Basement-membrane; Matrix; Regeneration; Quantification; Mechanisms; Epithelium
ISSN (print) / ISBN 1744-4292
e-ISSN 1744-4292
Zeitschrift Molecular Systems Biology
Quellenangaben Band: 11, Heft: 7, Seiten: , Artikelnummer: 819 Supplement: ,
Verlag EMBO Press
Begutachtungsstatus