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.
abstract: 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).
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Second Department of Internal Medicine, Tottori University School of Medicine, Yonago, Tottori, Japan.
authors.forename: Kinya
authors.initials: K
authors.lastname: Okamoto
authors.affiliation: Second Department of Internal Medicine, Tottori University School of Medicine, Yonago, Tottori, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Koda
authors.affiliation: Second Department of Internal Medicine, Tottori University School of Medicine, Yonago, Tottori, Japan.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Okamoto
authors.affiliation: Second Department of Internal Medicine, Tottori University School of Medicine, Yonago, Tottori, Japan.
authors.forename: Takumi
authors.initials: T
authors.lastname: Onoyama
authors.affiliation: Second Department of Internal Medicine, Tottori University School of Medicine, Yonago, Tottori, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Miyoshi
authors.affiliation: Second Department of Internal Medicine, Tottori University School of Medicine, Yonago, Tottori, Japan.
authors.forename: Manabu
authors.initials: M
authors.lastname: Kishina
authors.affiliation: Second Department of Internal Medicine, Tottori University School of Medicine, Yonago, Tottori, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Kato
authors.affiliation: Second Department of Internal Medicine, Tottori University School of Medicine, Yonago, Tottori, Japan.
authors.forename: Shiho
authors.initials: S
authors.lastname: Tokunaga
authors.affiliation: Second Department of Internal Medicine, Tottori University School of Medicine, Yonago, Tottori, Japan.
authors.forename: Taka-Aki
authors.initials: TA
authors.lastname: Sugihara
authors.affiliation: Department of Hepatology and Pancreatology, Kawasaki Medical School, Kurashiki, Okayama, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Hara
authors.affiliation: Department of Hepatology and Pancreatology, Kawasaki Medical School, Kurashiki, Okayama, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Hino
authors.affiliation: Second Department of Internal Medicine, Tottori University School of Medicine, Yonago, Tottori, Japan.
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Murawaki
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics*; D004195:Disease Models, Animal; D005234:Fatty Liver / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D065626:Non-alcoholic Fatty Liver Disease / Q000235:genetics* / Q000473:pathology*; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012984:Software
chemical_list: D015415:Biomarkers; D035683:MicroRNAs