Comparative Proteomic Analysis of Bleomycin-induced Pulmonary Fibrosis Based on Isobaric Tag for Quantitation

Am J Med Sci. 2017 Jan;353(1):49-58. doi: 10.1016/j.amjms.2016.11.021. Epub 2016 Nov 18.

Abstract

Background: Pulmonary fibrosis (PF) is a destructive pulmonary disease and the molecular mechanisms underlying PF are unclear. This study investigated differentially expressed proteins associated with the occurrence and development of PF in rat lung tissue with bleomycin-induced PF.

Methods: Sixteen Sprague-Dawley rats were randomly divided into 2 groups: the PF model group (n = 8) and the control group (n = 8). After successfully establishing the rat PF model induced by bleomycin, the differentially expressed proteins in the 2 groups were identified through isobaric tag for relative and absolute quantitation coupled with liquid chromatography-mass spectrometry and bioinformatics analysis.

Results: A total of 146 differentially expressed proteins were identified; 88 of which displayed increased abundance and 58 were downregulated in the PF rat model group. Most functional proteins were associated with extracellular matrix, inflammation, damage response, vitamin A synthesis and metabolism. Critical proteins related to PF development and progression was identified, such as type V collagen-3, arachidonic acid 12-lipoxygenase, arachidonic acid 15-lipoxygenase and cytochrome P4501A1. Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that these differentially expressed proteins were enriched in extracellular matrix receptor interaction pathway, renin-angiotensin system and metabolic pathway of retinol.

Conclusions: The proteins expressed in bleomycin-induced PF rat model provide important data for further functional analysis of proteins involved in PF.

Keywords: Bleomycin; Isobaric tag for relative and absolute quantitation; Proteome; Pulmonary fibrosis; Rat model.

MeSH terms

  • Animals
  • Bleomycin
  • Chromatography, Liquid
  • Cytochrome P-450 CYP1A1 / genetics
  • Cytochrome P-450 CYP1A1 / metabolism
  • Hydroxyproline / metabolism
  • Lung / metabolism
  • Lung / pathology
  • Male
  • Proteomics / methods*
  • Pulmonary Fibrosis / chemically induced
  • Pulmonary Fibrosis / metabolism*
  • Pulmonary Fibrosis / pathology
  • Rats, Sprague-Dawley
  • Tandem Mass Spectrometry

Substances

  • Bleomycin
  • Cytochrome P-450 CYP1A1
  • Hydroxyproline