Metabolomic profiling in a Hedgehog Interacting Protein (Hhip) murine model of chronic obstructive pulmonary disease

Abstract Genetic variants annotated to the hedgehog interacting protein (HHIP) are robustly associated with chronic obstructive pulmonary disease (COPD). Hhip haploinsufficiency in mice leads to increased susceptibility towards the development of emphysema following exposure to chronic cigarette smo...

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Autores principales:	Emily S. Wan, Yan Li, Taotao Lao, Weiliang Qiu, Zhiqiang Jiang, John D. Mancini, Caroline A. Owen, Clary Clish, Dawn L. DeMeo, Edwin K. Silverman, Xiaobo Zhou
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/487ff678e8004996a3d6158b2118fde2
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spelling	oai:doaj.org-article:487ff678e8004996a3d6158b2118fde22021-12-02T12:32:02ZMetabolomic profiling in a Hedgehog Interacting Protein (Hhip) murine model of chronic obstructive pulmonary disease10.1038/s41598-017-02701-42045-2322https://doaj.org/article/487ff678e8004996a3d6158b2118fde22017-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-02701-4https://doaj.org/toc/2045-2322Abstract Genetic variants annotated to the hedgehog interacting protein (HHIP) are robustly associated with chronic obstructive pulmonary disease (COPD). Hhip haploinsufficiency in mice leads to increased susceptibility towards the development of emphysema following exposure to chronic cigarette smoke (CS). To explore the molecular pathways which contribute to increased susceptibility, we performed metabolomic profiling using high performance liquid chromatography tandem mass spectroscopy (LC/MS-MS) on plasma, urine, and lung tissue of Hhip +/− heterozygotes and wild type (Hhip +/+) C57/BL6 mice exposed to either room-air or CS for six months. Univariate comparisons between groups were made with a combined fold change ≥2 and Student’s t-test p-value < 0.05 to denote significance; associations with mean alveolar chord length (MACL), a quantitative measure of emphysema, and gene-by-environment interactions were examined using empiric Bayes-mediated linear models. Decreased urinary excretion of cotinine despite comparable plasma levels was observed in Hhip +/− heterozygotes; a strong gene-by-smoking association was also observed. Correlations between MACL and markers of oxidative stress such as urinary methionine sulfoxide were observed in Hhip +/− but not in Hhip +/+ mice. Metabolite set enrichment analyses suggest reduced antioxidant capacity and alterations in macronutrient metabolism contribute to increased susceptibility to chronic CS-induced oxidative stress in Hhip haploinsufficiency states.Emily S. WanYan LiTaotao LaoWeiliang QiuZhiqiang JiangJohn D. ManciniCaroline A. OwenClary ClishDawn L. DeMeoEdwin K. SilvermanXiaobo ZhouNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Emily S. Wan Yan Li Taotao Lao Weiliang Qiu Zhiqiang Jiang John D. Mancini Caroline A. Owen Clary Clish Dawn L. DeMeo Edwin K. Silverman Xiaobo Zhou Metabolomic profiling in a Hedgehog Interacting Protein (Hhip) murine model of chronic obstructive pulmonary disease
description	Abstract Genetic variants annotated to the hedgehog interacting protein (HHIP) are robustly associated with chronic obstructive pulmonary disease (COPD). Hhip haploinsufficiency in mice leads to increased susceptibility towards the development of emphysema following exposure to chronic cigarette smoke (CS). To explore the molecular pathways which contribute to increased susceptibility, we performed metabolomic profiling using high performance liquid chromatography tandem mass spectroscopy (LC/MS-MS) on plasma, urine, and lung tissue of Hhip +/− heterozygotes and wild type (Hhip +/+) C57/BL6 mice exposed to either room-air or CS for six months. Univariate comparisons between groups were made with a combined fold change ≥2 and Student’s t-test p-value < 0.05 to denote significance; associations with mean alveolar chord length (MACL), a quantitative measure of emphysema, and gene-by-environment interactions were examined using empiric Bayes-mediated linear models. Decreased urinary excretion of cotinine despite comparable plasma levels was observed in Hhip +/− heterozygotes; a strong gene-by-smoking association was also observed. Correlations between MACL and markers of oxidative stress such as urinary methionine sulfoxide were observed in Hhip +/− but not in Hhip +/+ mice. Metabolite set enrichment analyses suggest reduced antioxidant capacity and alterations in macronutrient metabolism contribute to increased susceptibility to chronic CS-induced oxidative stress in Hhip haploinsufficiency states.
format	article
author	Emily S. Wan Yan Li Taotao Lao Weiliang Qiu Zhiqiang Jiang John D. Mancini Caroline A. Owen Clary Clish Dawn L. DeMeo Edwin K. Silverman Xiaobo Zhou
author_facet	Emily S. Wan Yan Li Taotao Lao Weiliang Qiu Zhiqiang Jiang John D. Mancini Caroline A. Owen Clary Clish Dawn L. DeMeo Edwin K. Silverman Xiaobo Zhou
author_sort	Emily S. Wan
title	Metabolomic profiling in a Hedgehog Interacting Protein (Hhip) murine model of chronic obstructive pulmonary disease
title_short	Metabolomic profiling in a Hedgehog Interacting Protein (Hhip) murine model of chronic obstructive pulmonary disease
title_full	Metabolomic profiling in a Hedgehog Interacting Protein (Hhip) murine model of chronic obstructive pulmonary disease
title_fullStr	Metabolomic profiling in a Hedgehog Interacting Protein (Hhip) murine model of chronic obstructive pulmonary disease
title_full_unstemmed	Metabolomic profiling in a Hedgehog Interacting Protein (Hhip) murine model of chronic obstructive pulmonary disease
title_sort	metabolomic profiling in a hedgehog interacting protein (hhip) murine model of chronic obstructive pulmonary disease
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/487ff678e8004996a3d6158b2118fde2
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Metabolomic profiling in a Hedgehog Interacting Protein (Hhip) murine model of chronic obstructive pulmonary disease

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