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Quantitative proteomic characterization of the lung extracellular matrix in chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis.

Type Information
Nr 63 (Research article)
Authors Åhrman, Emma; Hallgren, Oskar; Malmström, Lars; Hedström, Ulf; Malmström, Anders; Bjermer, Leif; Zhou, Xiao-Hong; Westergren-Thorsson, Gunilla; Malmström, Johan
Title Quantitative proteomic characterization of the lung extracellular matrix in chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis.
Journal J Proteomics (2018) 189 23-33
DOI 10.1016/j.jprot.2018.02.027
Citations 22 citations (journal impact: 4.27)
Abstract Remodeling of the extracellular matrix ECM is a common feature in lung diseases such as chronic obstructive pulmonary disease COPD and idiopathic pulmonary fibrosis IPF. Here we applied a sequential tissue extraction strategy to describe disease-specific remodeling of human lung tissue in disease using end-stages of COPD and IPF. Our strategy was based on quantitative comparison of the disease proteomes with specific focus on the matrisome using data-independent acquisition and targeted data analysis SWATH-MS. Our work provides an in-depth proteomic characterization of human lung tissue during impaired tissue remodeling. In addition we show important quantitative and qualitative effects of the solubility of matrisome proteins. COPD was characterized by a disease-specific increase in ECM regulators metalloproteinase inhibitor 3 TIMP3 and matrix metalloproteinase 28 MMP-28 whereas for IPF impairment in cell adhesion proteins such as collagen VI and laminins was most prominent. For both diseases we identified increased levels of proteins involved in the regulation of endopeptidase activity with several proteins belonging to the serpin family. The established human lung quantitative proteome inventory and the construction of a tissue-specific protein assay library provides a resource for future quantitative proteomic analyses of human lung tissues.