Time- and Compartment-resolved Proteome Profiling of the Extracellular Niche in Lung Injury and Repair

Overview

Journal Mol Syst Biol

Specialty Molecular Biology

Date 2015 Jul 16

PMID 26174933

Citations 134

Authors

Herbert B Schiller

Isis E Fernandez

Gerald Burgstaller

Christoph Schaab

Richard A Scheltema

Thomas Schwarzmayr

Tim M Strom

Oliver Eickelberg

Matthias Mann

Affiliations

Soon will be listed here.

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.

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