Abstract
Evidence indicates that hepatic fibrosis is the initial lesion of cirrhosis or hepatocellular carcinoma in diseases such as nonalcoholic steatohepatitis (NASH). To induce NASH, we fed rats a choline-deficient and iron-supplemented L-amino acid-defined (CDAA) diet. Histopathological examination revealed that fibrosis appeared from week 4 and progressed to bridging fibrosis from week 12. Using qRT-PCR assays, we detected increased expression of miR-21, Mmp-9, and Timp-1 in liver that peaked during week 4, when fibrosis was first detected. The expression pattern of miR-21 in plasma paralleled that in liver. Fibrosis tended to be resolved within 12 weeks of a recovery period after 12 weeks of feeding, and the expression of miR-21, Timp-1, and Mmp-9 decreased in liver. Comprehensive analyses of miRNA and mRNA expression in the liver using samples acquired at week 4 detected 16 miRNAs and 11 mRNAs that are mutually-interacting fibrosis-related factors. We therefore conclude that miR-21 was closely associated with fibrosis in a rat model of NASH and has potential as a plasma biomarker for hepatic fibrosis.
Keywords:
CDAA; Fibrosis; MiR-21; NASH.
Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
MeSH terms
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Animals
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Biomarkers / blood
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Choline / therapeutic use
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Choline Deficiency / complications
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Choline Deficiency / diet therapy
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Choline Deficiency / etiology
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Choline Deficiency / physiopathology
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Diet / adverse effects
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Dietary Supplements / poisoning
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Disease Models, Animal*
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Disease Progression
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Gene Expression Profiling
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Gene Expression Regulation
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Iron Overload / complications
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Iron Overload / etiology
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Iron Overload / physiopathology
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Iron, Dietary / poisoning
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Liver / immunology
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Liver / metabolism*
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Liver / pathology
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Liver / physiopathology
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Liver Cirrhosis / etiology*
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Liver Cirrhosis / prevention & control
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Matrix Metalloproteinase 9 / genetics
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Matrix Metalloproteinase 9 / metabolism*
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MicroRNAs / blood
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MicroRNAs / metabolism*
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Non-alcoholic Fatty Liver Disease / etiology
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Non-alcoholic Fatty Liver Disease / metabolism*
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Non-alcoholic Fatty Liver Disease / pathology
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Non-alcoholic Fatty Liver Disease / physiopathology
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RNA, Messenger / metabolism
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Rats, Wistar
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Specific Pathogen-Free Organisms
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Tissue Inhibitor of Metalloproteinase-1 / genetics
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Tissue Inhibitor of Metalloproteinase-1 / metabolism*
Substances
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Biomarkers
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Iron, Dietary
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MicroRNAs
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RNA, Messenger
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TIMP1 protein, rat
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Tissue Inhibitor of Metalloproteinase-1
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mirn21 microRNA, rat
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Matrix Metalloproteinase 9
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Mmp9 protein, rat
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Choline