RT Journal Article
SR Electronic
T1 Metabolic heterogeneity of idiopathic pulmonary fibrosis: a metabolomic study
JF BMJ Open Respiratory Research
JO BMJ Open Resp Res
FD British Thoracic Society
SP e000183
DO 10.1136/bmjresp-2017-000183
VO 4
IS 1
A1 Yidan D Zhao
A1 Li Yin
A1 Stephen Archer
A1 Catherine Lu
A1 George Zhao
A1 Yan Yao
A1 Licun Wu
A1 Michael Hsin
A1 Thomas K Waddell
A1 Shaf Keshavjee
A1 John Granton
A1 Marc de Perrot
YR 2017
UL http://bmjopenrespres.bmj.com/content/4/1/e000183.abstract
AB Introduction Idiopathic pulmonary fibrosis (IPF) is a chronic and fatal disease of unknown cause characterised by progressive fibrotic formation in lung tissue. We hypothesise that disrupted metabolic pathways in IPF contribute to disease pathogenesis.Methods Metabolomics of human IPF was performed using mass spectroscopy (IPF lung=8; donor lung=8). Gene expression of key metabolic enzymes was measured using microarrays. Of the 108 metabolites whose levels were found altered, 48 were significantly increased, whereas 60 were significantly decreased in IPF samples compared with normal controls.Results Specific metabolic pathways mediating the IPF remodelling were found with a downregulated sphingolipid metabolic pathway but an upregulated arginine pathway in IPF. In addition, disrupted glycolysis, mitochondrial beta-oxidation and tricarboxylic acid cycle, altered bile acid, haem and glutamate/aspartate metabolism were found in IPF samples compared with control.Conclusions Our results show alterations in metabolic pathways for energy consumption during lung structural remodelling, which may contribute to IPF pathogenesis. We believe that this is the first report of simultaneously and systemically measuring changes of metabolites involving nine metabolic pathways in human severe IPF lungs. The measurement of the metabolites may serve in the future diagnosis and prognosis of IPF.