Abstract
BackgroundIdiopathic pulmonary fibrosis (IPF) is a progressive, eventually fatal disease. IPF is characterized by excessive accumulation of the extracellular matrix (ECM) in the alveolar parenchyma and progressive lung scarring. The pathogenesis of IPF and whether the ECM involved in the process remain unknown.MethodsTo identify potential treatment target and ECM associated proteins that may be involved in the development of IPF, we employed isobaric tag for relative and absolute quantitation (iTRAQ) combined liquid chromatography–tandem mass spectrometry (LC–MS/MS) approach to examine protein expression in lung tissues from IPF patients.ResultsA total of 662 proteins with altered expression (455 upregulated proteins and 207 downregulated proteins) were identified in lung tissue of IPF patients compared with control. KEGG pathway enrichment analysis showed that the altered proteins in lung tissue mainly belonged to the PI3K-Akt signaling, focal adhesion, ECM-receptor interaction, and carbon metabolism pathways. According to the bioinformatic definition of the matrisome, 229 matrisome proteins were identified in lung tissue. These proteins comprised the ECM of lung, of which 104 were core matrisome proteins, and 125 were matrisome-associated proteins. Of the 229 ECM quantified proteins, 56 significantly differentially expressed proteins (19 upregulated proteins and 37 downregulated proteins) were detected in IPF lung tissue samples. In addition to proteins with well-known functions such as COL1A1, SCGB1A1, TAGLN, PSEN2, TSPAN1, CTSB, AGR2, CSPG2, and SERPINB3, we identified several novel ECM proteins with unknown function deposited in IPF lung tissue including LGALS7, ASPN, HSP90AA1 and HSP90AB1. Some of these differentially expressed proteins were further verified using Western blot analysis and immunohistochemical staining.ConclusionsThis study provides a list of proteomes that were detected in IPF lung tissue by iTRAQ technology combined with LC–MS/MS. The findings of this study will contribute better understanding to the pathogenesis of IPF and facilitate the development of therapeutic targets.
Highlights
Idiopathic pulmonary fibrosis (IPF) is a progressive, eventually fatal disease
Identification and functional ontology classification of differentially expressed proteins A total of 4241 proteins were identified in the lung tissue samples from IPF patients and controls, matched in database, more details were supplied in Additional file 1: Table S1
Among the 662 differentially expressed proteins, 229 extracellular matrix (ECM) proteins were identified as matrisome proteins in normal and IPF lungs, including 104 core ECM proteins and 125 ECM-related proteins (Table 1)
Summary
Idiopathic pulmonary fibrosis (IPF) is a progressive, eventually fatal disease. IPF is characterized by excessive accumulation of the extracellular matrix (ECM) in the alveolar parenchyma and progressive lung scarring. IPF is characterized by scarring fibrosis with a median survival of 2–3 years after diagnosis and has an unpredictable progression [1,2,3] This high mortality rate and relatively few therapeutic options are partly due to an incomplete understanding of the molecular mechanisms behind the disease [4, 5]. Recent study have focused on metabolic changes in bleomycin-treated mouse lung and IPF patient lung, proteomic analysis was performed on these lung tissues. They observed reduced glycolysis/ gluconeogenesis and enhanced ascorbate and aldarate metabolism, and the imbalanced metabolism can be restored by pirfenidone [16]. Proteome analysis for human lung and skin fibrosis reveals surprisingly high prevalence of marginal zone B- and B1-cell-specific protein (MZB1)-positive plasma B cells both in lung and skin fibrosis [19]
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