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

Journal of Cellular and Molecular Medicine

Ewa E. Hennig¹  Michal Mikula²  Krzysztof Goryca²  Agnieszka Paziewska¹  Joanna Ledwon¹  Monika Nesteruk¹  Marek Woszczynski²  Bozena Walewska-Zielecka³  Kazimiera Pysniak² 

[1] Department of Gastroenterology and Hepatology, Medical Center for Postgraduate Education, Warsaw, Poland;Department of Genetics, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland;Department of Public Health, Health Sciences Faculty, Warsaw Medical University, Warsaw, Poland

关键词: steatosis;    steatohepatitis;    NAFLD;    NASH;    obesity;    transcriptomics;    liver;    mouse model;    extracellular matrix;    cytochrome P450;   

DOI  :  10.1111/jcmm.12328

来源: Wiley

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2014 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

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