MicroRNA expression profiles related to early stage murine concanavalin A-induced hepatitis

Cell Physiol Biochem. 2014;33(6):1933-44. doi: 10.1159/000362970. Epub 2014 Jun 27.

Abstract

Background: Fulminant hepatitis is a severe liver disease characterized by massive hepatocyte necrosis and clinical signs of liver failure. This study explores the expression profile of microRNAs, which are regulators of a number of pathophysiological processes, during the early stage of concanavalin A (Con A)-induced hepatitis.

Methods: Balb/c mice were given ConA injections to induce fulminant hepatitis. miRNA expression profiling in liver tissues was carried out by microarray analysis. The differentially expressed miRNAs were subjected to time sequence profile analysis, gene-miRNA regulatory network analysis, and gene ontology-miRNA regulatory network analysis.

Results: Eleven miRNAs among multiClass were found to be significantly differentially expressed between liver tissue in early stage fulminant hepatitis and normal control liver tissue. Mmu-miR-133a was the most differentially expressed with the strongest regulatory ability, regulating 47 mRNAs. Mmu-miR-10a was the most highly expressed in the microRNA-GO-Network and also exerted a strong regulatory ability. The expression profiles of miR-133a and miR-10a were verified by RT-PCR.

Conclusions: These results show that, in the early stage, ConA-induced fulminant hepatitis induces a distinct miRNA expression profile. This differential miRNA expression profile may provide pathogenic clues and potential diagnostic and prognostic markers in acute and severe liver disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alanine Transaminase / blood
  • Animals
  • Aspartate Aminotransferases / blood
  • Bilirubin / blood
  • Chemical and Drug Induced Liver Injury / blood
  • Chemical and Drug Induced Liver Injury / etiology
  • Chemical and Drug Induced Liver Injury / genetics*
  • Concanavalin A
  • Gene Ontology
  • Gene Regulatory Networks
  • L-Lactate Dehydrogenase / blood
  • Liver / metabolism*
  • Liver / pathology
  • Male
  • Mice, Inbred BALB C
  • MicroRNAs / genetics*
  • Models, Genetic
  • Oligonucleotide Array Sequence Analysis
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transcriptome*

Substances

  • MicroRNAs
  • Concanavalin A
  • L-Lactate Dehydrogenase
  • Aspartate Aminotransferases
  • Alanine Transaminase
  • Bilirubin