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
Pages (from-to)2965-2978
Number of pages14
JournalJournal of Proteome Research
Volume18
Issue number7
DOIs
Publication statusPublished - Jul 5 2019

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Chemistry(all)

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