Metabolic heterogeneity of idiopathic pulmonary fibrosis: a metabolomic study
YD Zhao, L Yin, S Archer, C Lu… - BMJ open …, 2017 - bmjopenrespres.bmj.com
YD Zhao, L Yin, S Archer, C Lu, G Zhao, Y Yao, L Wu, M Hsin, TK Waddell, S Keshavjee…
BMJ open respiratory research, 2017•bmjopenrespres.bmj.comIntroduction 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 …
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 …
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.
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