title: Metabolic Profiling Regarding Pathogenesis of Idiopathic Pulmonary Fibrosis.
abstract: Idiopathic pulmonary fibrosis (IPF) is a progressive, eventually fatal disease characterized by fibrosis of the lung parenchyma and loss of lung function. IPF is believed to be caused by repetitive alveolar epithelial cell injury and dysregulated repair process including uncontrolled proliferation of lung (myo) fibroblasts and excessive deposition of extracellular matrix proteins in the interstitial space; however, the pathogenic pathways involved in IPF have not been fully elucidated. In this study, we attempted to characterize metabolic changes of lung tissues involved in the pathogenesis of IPF using gas chromatography-mass spectrometry-based metabolic profiling. Partial least-squares discriminant analysis (PLS-DA) model generated from metabolite data was able to discriminate between the control subjects and IPF patients (R(2)X = 0.37, R(2)Y = 0.613 and Q(2) (cumulative) = 0.54, receiver operator characteristic AUC > 0.9). We discovered 25 metabolite signatures of IPF using both univariate and multivariate statistical analyses (FDR < 0.05 and VIP score of PLS-DA > 1). These metabolite signatures indicated alteration in metabolic pathways: adenosine triphosphate degradation pathway, glycolysis pathway, glutathione biosynthesis pathway, and ornithine aminotransferase pathway. The results could provide additional insight into understanding the disease and potential for developing biomarkers.
authors.affiliation: College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University , 1 Gwanak-ro, Gwanak-gu, Seoul 08826, Korea.
authors.forename: Yun Pyo
authors.initials: YP
authors.lastname: Kang
authors.affiliation: College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University , 1 Gwanak-ro, Gwanak-gu, Seoul 08826, Korea.
authors.forename: Sae Bom
authors.initials: SB
authors.lastname: Lee
authors.affiliation: Division of Allergy and Respiratory Medicine, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital , 1174, Jung- Dong, Wonmi-Ku, Bucheon, Gyeonggi-Do 420-767, Korea.
authors.forename: Ji-Min
authors.initials: JM
authors.lastname: Lee
authors.affiliation: College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University , 1 Gwanak-ro, Gwanak-gu, Seoul 08826, Korea.
authors.forename: Hyung Min
authors.initials: HM
authors.lastname: Kim
authors.affiliation: College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University , 1 Gwanak-ro, Gwanak-gu, Seoul 08826, Korea.
authors.forename: Ji Yeon
authors.initials: JY
authors.lastname: Hong
authors.affiliation: College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University , 1 Gwanak-ro, Gwanak-gu, Seoul 08826, Korea.
authors.forename: Won Jun
authors.initials: WJ
authors.lastname: Lee
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, Soonchunhyang University Bucheon Hospital , 1174, Jung- Dong, Wonmi-Ku, Bucheon, Gyeonggi-Do 420-767, Korea.
authors.forename: Chang Woo
authors.initials: CW
authors.lastname: Choi
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, Soonchunhyang University Bucheon Hospital , 1174, Jung- Dong, Wonmi-Ku, Bucheon, Gyeonggi-Do 420-767, Korea.
authors.forename: Hwa Kyun
authors.initials: HK
authors.lastname: Shin
authors.affiliation: Division of Allergy and Respiratory Medicine, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital , 1174, Jung- Dong, Wonmi-Ku, Bucheon, Gyeonggi-Do 420-767, Korea.
authors.forename: Do-Jin
authors.initials: DJ
authors.lastname: Kim
authors.affiliation: Department of Pathology, Soonchunhyang University Bucheon Hospital , 1174, Jung- Dong, Wonmi-Ku, Bucheon, Gyeonggi-Do 420-767, Korea.
authors.forename: Eun Suk
authors.initials: ES
authors.lastname: Koh
authors.affiliation: Division of Allergy and Respiratory Medicine, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital , 1174, Jung- Dong, Wonmi-Ku, Bucheon, Gyeonggi-Do 420-767, Korea.
authors.forename: Choon-Sik
authors.initials: CS
authors.lastname: Park
authors.affiliation: College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University , 1 Gwanak-ro, Gwanak-gu, Seoul 08826, Korea.
authors.forename: Sung Won
authors.initials: SW
authors.lastname: Kwon
authors.affiliation: Division of Allergy and Respiratory Medicine, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital , 1174, Jung- Dong, Wonmi-Ku, Bucheon, Gyeonggi-Do 420-767, Korea.
authors.forename: Sung-Woo
authors.initials: SW
authors.lastname: Park
mesh_terms: D016022:Case-Control Studies; D002478:Cells, Cultured; D016002:Discriminant Analysis; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000378:metabolism* / Q000473:pathology; D053858:Metabolic Networks and Pathways; D055432:Metabolomics / Q000379:methods*; D058628:Myofibroblasts / Q000378:metabolism / Q000473:pathology
keywords: gas chromatography−mass spectrometry (GC−MS); idiopathic pulmonary fibrosis; lung tissue; metabolic profiling