Extracellular matrix and cytochrome P450 gene expression can distinguish steatohepatitis from steatosis in mice
Article first published online: 9 JUN 2014
© 2014 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Journal of Cellular and Molecular Medicine
Volume 18, Issue 9, pages 1762–1772, September 2014
How to Cite
Hennig, E. E., Mikula, M., Goryca, K., Paziewska, A., Ledwon, J., Nesteruk, M., Woszczynski, M., Walewska-Zielecka, B., Pysniak, K. and Ostrowski, J. (2014), Extracellular matrix and cytochrome P450 gene expression can distinguish steatohepatitis from steatosis in mice. Journal of Cellular and Molecular Medicine, 18: 1762–1772. doi: 10.1111/jcmm.12328
- Issue published online: 10 SEP 2014
- Article first published online: 9 JUN 2014
- Manuscript Accepted: 15 APR 2014
- Manuscript Received: 31 JAN 2014
- Polish Ministry of Science and Higher Education. Grant Numbers: NN401 017436, NN401 532240
- NAFLD ;
- NASH ;
- mouse model;
- extracellular matrix;
- cytochrome P450
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.