RRC ID 36685
Author Okamoto K, Koda M, Okamoto T, Onoyama T, Miyoshi K, Kishina M, Kato J, Tokunaga S, Sugihara TA, Hara Y, Hino K, Murawaki Y.
Title A Series of microRNA in the Chromosome 14q32.2 Maternally Imprinted Region Related to Progression of Non-Alcoholic Fatty Liver Disease in a Mouse Model.
Journal PLoS One
Abstract BACKGROUND & AIMS:Simple steatosis (SS) and non-alcoholic steatohepatitis (NASH) are subtypes of non-alcoholic fatty liver disease (NAFLD), and the pathogenic differences between SS and NASH remain unclear. MicroRNAs (miRNAs) are endogenous, non-coding, short RNAs that regulate gene expression. The aim of this study was to use animal models and human samples to examine the relationship between miRNA expression profiles and each type of NAFLD (SS and NASH).
METHODS:DD Shionogi, Fatty Liver Shionogi (FLS) and FLS ob/ob mice were used as models for normal control, SS and NASH, respectively. Microarray analysis and real-time PCR were used to identify candidate NAFLD-related miRNAs. Human serum samples were used to examine the expression profiles of these candidate miRNAs in control subjects and patients with SS or NASH.
RESULTS:Fourteen miRNAs showed clear expression differences among liver tissues from SS, NASH, and control mice with good reproducibility. Among these NAFLD candidate miRNAs, seven showed similar expression patterns and were upregulated in both SS and NASH tissues; these seven candidate miRNAs mapped to an miRNA cluster in the 14q32.2 maternally imprinted region delineated by delta-like homolog 1 and type III iodothyronine deiodinase (Dlk1-Dio3 mat). Software-based predictions indicated that the transforming growth factor-β pathway, insulin like growth factor-1 and 5' adenosine monophosphate activated protein kinase were potential targets of theses Dlk1-Dio3 mat NAFLD candidate miRNAs. In addition, serum samples from patients with SS or NASH differed markedly with regard to expression of the putative Dlk1-Dio3 mat miRNAs, and these differences accurately corresponded with NAFLD diagnosis.
CONCLUSION:The expression profiles of seven miRNAs in 14q32.2 mat have high potential as biomarkers for NAFLD and for improving future research on the pathogenesis and treatment of NASH.
Volume 11(5)
Pages e0154676
Published 2016-1-1
DOI 10.1371/journal.pone.0154676
PII PONE-D-15-50033
PMID 27135827
PMC PMC4852931
MeSH Animals Biomarkers / metabolism Chromosomes, Human, Pair 14 / genetics* Disease Models, Animal Fatty Liver / genetics* Fatty Liver / pathology Humans Liver / metabolism* Male Mice MicroRNAs / genetics* Non-alcoholic Fatty Liver Disease / genetics* Non-alcoholic Fatty Liver Disease / pathology* Oligonucleotide Array Sequence Analysis Reverse Transcriptase Polymerase Chain Reaction Software
IF 2.74
Times Cited 10
Mice RBRC03706