Extracellular matrix and cytochrome P450 gene expression can distinguish steatohepatitis from steatosis in mice

Ewa E. Hennig, Michal Mikula, Krzysztof Goryca, Agnieszka Paziewska, Joanna Karolina Ledwon, Monika Nesteruk, Marek Woszczynski, Bozena Walewska-Zielecka, Kazimiera Pysniak, Jerzy Ostrowski*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

One of the main questions regarding nonalcoholic fatty liver disease is the molecular background of the transition from simple steatosis (SS) to the inflammatory and fibrogenic condition of steatohepatitis (NASH). We examined the gene expression changes during progression from histologically normal liver to SS and NASH in models of obesity caused by hyperphagia or a high-fat diet. Microarray-based analysis revealed that the expression of 1445 and 264 probe sets was changed exclusively in SS and NASH samples, respectively, and 1577 probe sets were commonly altered in SS and NASH samples. Functional annotations indicated that transcriptome alterations that were common for NASH and SS, as well as exclusive for NASH, involved extracellular matrix (ECM)-related processes, although they differed in the type of matrix structure change. The expression of 80 genes was significantly changed in all three comparisons: SS versus control, NASH versus control and NASH versus SS. Of these genes, epithelial membrane protein 1, IKBKB interacting protein and decorin were progressively up-regulated in both SS and NASH compared to normal tissue. The molecular context of interactions of encoded 80 proteins revealed that they are highly interconnected and significantly enriched for processes involving metabolism by cytochrome P450. Validation of 10 selected mRNAs encoding genes related to ECM and cytochrome P450 with quantitative RT-PCR analysis showed consistent changes in their expression during NASH development. The expression profile of these genes has the potential to distinguish NASH from SS and normal tissue and may possibly be beneficial in the clinical diagnosis of NASH.

Original languageEnglish (US)
Pages (from-to)1762-1772
Number of pages11
JournalJournal of Cellular and Molecular Medicine
Volume18
Issue number9
DOIs
StatePublished - Sep 1 2014

Keywords

  • Cytochrome P450
  • Extracellular matrix
  • Liver
  • Mouse model
  • NAFLD
  • NASH
  • Obesity
  • Steatohepatitis
  • Steatosis
  • Transcriptomics

ASJC Scopus subject areas

  • Molecular Medicine
  • Cell Biology

Fingerprint Dive into the research topics of 'Extracellular matrix and cytochrome P450 gene expression can distinguish steatohepatitis from steatosis in mice'. Together they form a unique fingerprint.

Cite this