NDLI: Nonalcoholic steatohepatitis is associated with altered hepatic MicroRNA expression.

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Nonalcoholic steatohepatitis is associated with altered hepatic MicroRNA expression.

Year: 2008 Volume: 48 Issue: 5

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Nonalcoholic steatohepatitis is associated with altered hepatic MicroRNA expression.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Cheung, Onpan Puri, Puneet Eicken, Christoph Contos, Melissa J. Mirshahi, Faridoddin Maher, James W. Kellum, John M. Min, Haeki Luketic, Velimir A. Sanyal, Arun J.
Description	Country affiliation: United States Author Affiliation: Cheung O ( Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, Virginia Commonwealth University Medical Center, Richmond, VA, USA.)
Abstract	UNLABELLED: The expression of microRNA in nonalcoholic steatohepatitis (NASH) and their role in the genesis of NASH are not known. The aims of this study were to: (1) identify differentially expressed microRNAs in human NASH, (2) tabulate their potential targets, and (3) define the effect of a specific differentially expressed microRNA, miR-122, on its targets and compare these effects with the pattern of expression of these targets in human NASH. The expression of 474 human microRNAs was compared in subjects with the metabolic syndrome and NASH versus controls with normal liver histology. Differentially expressed microRNAs were identified by the muParaflo microRNA microarray assay and validated using quantitative real-time polymerase chain reaction (PCR). The effects of a specific differentially expressed miRNA (miR-122) on its predicted targets were assessed by silencing and overexpressing miR-122 in vitro. A total of 23 microRNAs were underexpressed or overexpressed. The predicted targets of these microRNAs are known to affect cell proliferation, protein translation, apoptosis, inflammation, oxidative stress, and metabolism. The miR-122 level was significantly decreased in subjects with NASH (63% by real-time PCR, P < 0.00001). Silencing miR-122 led to an initial increase in mRNA levels of these targets (P < 0.05 for all) followed by a decrease by 48 hours. This was accompanied by an increase in protein levels of these targets (P < 0.05 for all). Overexpression of miR-122 led to a significant decrease in protein levels of these targets. CONCLUSIONS: NASH is associated with altered hepatic microRNA expression. Underexpression of miR-122 potentially contributes to altered lipid metabolism implicated in the pathogenesis of NASH.
File Format	HTM / HTML
ISSN	02709139
e-ISSN	15273350
DOI	10.1002/hep.22569
Journal	Hepatology
Issue Number	6
Volume Number	48
Language	English
Publisher	Wiley
Publisher Date	2008-12-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Discipline Hepatology Fatty Liver Metabolism Liver Micrornas Apoptosis Physiology Biopsy Case-control Studies Cell Proliferation Gene Silencing Lipid Metabolism Pathology Metabolic Syndrome X Oxidative Stress Research Support, N.i.h., Extramural Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article
Subject	Hepatology

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Nonalcoholic steatohepatitis is associated with altered hepatic MicroRNA expression.