A Proteomic Analysis of GSD-1a in Mouse Livers

Evidence for Metabolic Reprogramming, Inflammation, and Macrophage Polarization

Research output: Contribution to journalArticle

Abstract

Glycogen storage disease type 1a (GSD-1a) is a rare genetic disease caused by mutations in the catalytic subunit of the enzyme glucose-6-phosphatase-alpha (G6Pase-α). The majority of patients develop long-term complications including renal failure and hepatocellular adenoma/carcinoma. The purpose of this study was to ascertain the proteomic changes in the liver of LS-G6pc-/- mice, a murine model of GSD-1a, in comparison with wild type mice to identify potential biomarkers of the pathophysiology of the affected liver. We used liquid chromatography-tandem mass spectrometry (LC-MS/MS) to analyze liver lysates from a total of 20 LS-G6pc-/- and 18 wild type (WT) mice. We compared the proteomic expression profile of LS-G6pc-/- and WT mice. We identified 4138 significantly expressed proteins, 1243 of which were differentially represented. Network and pathway analyses indicate that LS-G6pc-/- livers display an age-dependent modulation of the expression of proteins involved in specific biological processes associated with increased progression of liver disease. Moreover, we found upregulation of proteins involved in the process of tissue inflammation and macrophage polarization toward the M2 phenotype in LS-G6pc-/- mice with adenomas. Our results identify a metabolic reprogramming of glucose-6-P and a pathologic environment in the liver compatible with tumor development and progression.

Original languageEnglish
JournalJournal of Proteome Research
DOIs
Publication statusPublished - Jan 1 2019

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Glycogen Storage Disease
Macrophages
Glycogen
Liver
Proteomics
Polarization
Inflammation
Liver Cell Adenoma
Biological Phenomena
Glucose-6-Phosphatase
Inborn Genetic Diseases
Proteins
Rare Diseases
Tandem Mass Spectrometry
Liquid Chromatography
Adenoma
Liquid chromatography
Biomarkers
Renal Insufficiency
Liver Diseases

Keywords

  • animal model
  • glycogen storage disease type 1a
  • hepatocellular adenoma
  • hypoxia
  • macrophage polarization
  • proteomics

ASJC Scopus subject areas

  • Biochemistry
  • Chemistry(all)

Cite this

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title = "A Proteomic Analysis of GSD-1a in Mouse Livers: Evidence for Metabolic Reprogramming, Inflammation, and Macrophage Polarization",
abstract = "Glycogen storage disease type 1a (GSD-1a) is a rare genetic disease caused by mutations in the catalytic subunit of the enzyme glucose-6-phosphatase-alpha (G6Pase-α). The majority of patients develop long-term complications including renal failure and hepatocellular adenoma/carcinoma. The purpose of this study was to ascertain the proteomic changes in the liver of LS-G6pc-/- mice, a murine model of GSD-1a, in comparison with wild type mice to identify potential biomarkers of the pathophysiology of the affected liver. We used liquid chromatography-tandem mass spectrometry (LC-MS/MS) to analyze liver lysates from a total of 20 LS-G6pc-/- and 18 wild type (WT) mice. We compared the proteomic expression profile of LS-G6pc-/- and WT mice. We identified 4138 significantly expressed proteins, 1243 of which were differentially represented. Network and pathway analyses indicate that LS-G6pc-/- livers display an age-dependent modulation of the expression of proteins involved in specific biological processes associated with increased progression of liver disease. Moreover, we found upregulation of proteins involved in the process of tissue inflammation and macrophage polarization toward the M2 phenotype in LS-G6pc-/- mice with adenomas. Our results identify a metabolic reprogramming of glucose-6-P and a pathologic environment in the liver compatible with tumor development and progression.",
keywords = "animal model, glycogen storage disease type 1a, hepatocellular adenoma, hypoxia, macrophage polarization, proteomics",
author = "Davide Cangelosi and Roberta Resaz and Andrea Petretto and Daniela Segalerba and Marzia Ognibene and Federica Raggi and Luca Mastracci and Federica Grillo and Bosco, {Maria Carla} and Luigi Varesio and Antonio Sica and Irma Colombo and Alessandra Eva",
year = "2019",
month = "1",
day = "1",
doi = "10.1021/acs.jproteome.9b00309",
language = "English",
journal = "Journal of Proteome Research",
issn = "1535-3893",
publisher = "American Chemical Society",

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TY - JOUR

T1 - A Proteomic Analysis of GSD-1a in Mouse Livers

T2 - Evidence for Metabolic Reprogramming, Inflammation, and Macrophage Polarization

AU - Cangelosi, Davide

AU - Resaz, Roberta

AU - Petretto, Andrea

AU - Segalerba, Daniela

AU - Ognibene, Marzia

AU - Raggi, Federica

AU - Mastracci, Luca

AU - Grillo, Federica

AU - Bosco, Maria Carla

AU - Varesio, Luigi

AU - Sica, Antonio

AU - Colombo, Irma

AU - Eva, Alessandra

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Glycogen storage disease type 1a (GSD-1a) is a rare genetic disease caused by mutations in the catalytic subunit of the enzyme glucose-6-phosphatase-alpha (G6Pase-α). The majority of patients develop long-term complications including renal failure and hepatocellular adenoma/carcinoma. The purpose of this study was to ascertain the proteomic changes in the liver of LS-G6pc-/- mice, a murine model of GSD-1a, in comparison with wild type mice to identify potential biomarkers of the pathophysiology of the affected liver. We used liquid chromatography-tandem mass spectrometry (LC-MS/MS) to analyze liver lysates from a total of 20 LS-G6pc-/- and 18 wild type (WT) mice. We compared the proteomic expression profile of LS-G6pc-/- and WT mice. We identified 4138 significantly expressed proteins, 1243 of which were differentially represented. Network and pathway analyses indicate that LS-G6pc-/- livers display an age-dependent modulation of the expression of proteins involved in specific biological processes associated with increased progression of liver disease. Moreover, we found upregulation of proteins involved in the process of tissue inflammation and macrophage polarization toward the M2 phenotype in LS-G6pc-/- mice with adenomas. Our results identify a metabolic reprogramming of glucose-6-P and a pathologic environment in the liver compatible with tumor development and progression.

AB - Glycogen storage disease type 1a (GSD-1a) is a rare genetic disease caused by mutations in the catalytic subunit of the enzyme glucose-6-phosphatase-alpha (G6Pase-α). The majority of patients develop long-term complications including renal failure and hepatocellular adenoma/carcinoma. The purpose of this study was to ascertain the proteomic changes in the liver of LS-G6pc-/- mice, a murine model of GSD-1a, in comparison with wild type mice to identify potential biomarkers of the pathophysiology of the affected liver. We used liquid chromatography-tandem mass spectrometry (LC-MS/MS) to analyze liver lysates from a total of 20 LS-G6pc-/- and 18 wild type (WT) mice. We compared the proteomic expression profile of LS-G6pc-/- and WT mice. We identified 4138 significantly expressed proteins, 1243 of which were differentially represented. Network and pathway analyses indicate that LS-G6pc-/- livers display an age-dependent modulation of the expression of proteins involved in specific biological processes associated with increased progression of liver disease. Moreover, we found upregulation of proteins involved in the process of tissue inflammation and macrophage polarization toward the M2 phenotype in LS-G6pc-/- mice with adenomas. Our results identify a metabolic reprogramming of glucose-6-P and a pathologic environment in the liver compatible with tumor development and progression.

KW - animal model

KW - glycogen storage disease type 1a

KW - hepatocellular adenoma

KW - hypoxia

KW - macrophage polarization

KW - proteomics

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U2 - 10.1021/acs.jproteome.9b00309

DO - 10.1021/acs.jproteome.9b00309

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JO - Journal of Proteome Research

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SN - 1535-3893

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