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Title: Plasma microRNAs are sensitive indicators of inter-strain differences in the severity of liver injury induced in mice by a choline- and folate-deficient diet

Abstract

MicroRNAs (miRNAs) are a class of small, conserved, tissue-specific regulatory non-coding RNAs that modulate a variety of biological processes and play a fundamental role in the pathogenesis of major human diseases, including nonalcoholic fatty liver disease (NAFLD). However, the association between inter-individual differences in susceptibility to NAFLD and altered miRNA expression is largely unknown. In view of this, the goals of the present study were (i) to determine whether or not individual differences in the extent of NAFLD-induced liver injury are associated with altered miRNA expression, and (ii) assess if circulating blood miRNAs may be used as potential biomarkers for the noninvasive evaluation of the severity of NAFLD. A panel of seven genetically diverse strains of inbred male mice (A/J, C57BL/6J, C3H/HeJ, 129S/SvImJ, CAST/EiJ, PWK/PhJ, and WSB/EiJ) were fed a choline- and folate-deficient (CFD) diet for 12 weeks. This diet induced liver injury in all mouse strains; however, the extent of NAFLD-associated pathomorphological changes in the livers was strain-specific, with A/J, C57BL/6J, and C3H/HeJ mice being the least sensitive and WSB/EiJ mice being the most sensitive. The morphological changes in the livers were accompanied by differences in the levels of hepatic and plasma miRNAs. The levels of circulating miR-34a, miR-122,more » miR-181a, miR-192, and miR-200b miRNAs were significantly correlated with a severity of NAFLD-specific liver pathomorphological features, with the strongest correlation occurring with miR-34a. These observations suggest that the plasma levels of miRNAs may be used as biomarkers for noninvasive monitoring the extent of NAFLD-associated liver injury and susceptibility to NAFLD. -- Highlights: ► Choline- and folate-deficiency induces a strain-specific fatty liver injury in mice. ► The extent of liver pathology was accompanied by the changes in microRNA expression. ► The levels of circulating microRNAs mirror the magnitude of fatty liver injury. ► Plasma microRNAs may be sensitive noninvasive indicators of the fatty liver injury.« less

Authors:
 [1];  [2];  [1];  [3];  [1];  [4];  [1]
  1. Division of Biochemical Toxicology, National Center for Toxicological Research, Jefferson, AR 72079 (United States)
  2. Toxicologic Pathology Associates, National Center for Toxicological Research, Jefferson, AR 72079 (United States)
  3. Division of Cancer Prevention, National Cancer Institute, Bethesda, MD 20892 (United States)
  4. Department of Environmental Sciences and Engineering, University of North Carolina, Chapel Hill, NC 27599 (United States)
Publication Date:
OSTI Identifier:
22215347
Resource Type:
Journal Article
Journal Name:
Toxicology and Applied Pharmacology
Additional Journal Information:
Journal Volume: 262; Journal Issue: 1; Other Information: Copyright (c) 2012 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0041-008X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ALANINES; BIOLOGICAL MARKERS; CHOLINE; INJURIES; LACTATE DEHYDROGENASE; LIVER; MICE; MORPHOLOGICAL CHANGES; POLYMERASE CHAIN REACTION; TRANSCRIPTION

Citation Formats

Tryndyak, Volodymyr P., Latendresse, John R., Montgomery, Beverly, Ross, Sharon A., Beland, Frederick A., Rusyn, Ivan, and Pogribny, Igor P., E-mail: igor.pogribny@fda.hhs.gov. Plasma microRNAs are sensitive indicators of inter-strain differences in the severity of liver injury induced in mice by a choline- and folate-deficient diet. United States: N. p., 2012. Web. doi:10.1016/J.TAAP.2012.04.018.
Tryndyak, Volodymyr P., Latendresse, John R., Montgomery, Beverly, Ross, Sharon A., Beland, Frederick A., Rusyn, Ivan, & Pogribny, Igor P., E-mail: igor.pogribny@fda.hhs.gov. Plasma microRNAs are sensitive indicators of inter-strain differences in the severity of liver injury induced in mice by a choline- and folate-deficient diet. United States. doi:10.1016/J.TAAP.2012.04.018.
Tryndyak, Volodymyr P., Latendresse, John R., Montgomery, Beverly, Ross, Sharon A., Beland, Frederick A., Rusyn, Ivan, and Pogribny, Igor P., E-mail: igor.pogribny@fda.hhs.gov. Sun . "Plasma microRNAs are sensitive indicators of inter-strain differences in the severity of liver injury induced in mice by a choline- and folate-deficient diet". United States. doi:10.1016/J.TAAP.2012.04.018.
@article{osti_22215347,
title = {Plasma microRNAs are sensitive indicators of inter-strain differences in the severity of liver injury induced in mice by a choline- and folate-deficient diet},
author = {Tryndyak, Volodymyr P. and Latendresse, John R. and Montgomery, Beverly and Ross, Sharon A. and Beland, Frederick A. and Rusyn, Ivan and Pogribny, Igor P., E-mail: igor.pogribny@fda.hhs.gov},
abstractNote = {MicroRNAs (miRNAs) are a class of small, conserved, tissue-specific regulatory non-coding RNAs that modulate a variety of biological processes and play a fundamental role in the pathogenesis of major human diseases, including nonalcoholic fatty liver disease (NAFLD). However, the association between inter-individual differences in susceptibility to NAFLD and altered miRNA expression is largely unknown. In view of this, the goals of the present study were (i) to determine whether or not individual differences in the extent of NAFLD-induced liver injury are associated with altered miRNA expression, and (ii) assess if circulating blood miRNAs may be used as potential biomarkers for the noninvasive evaluation of the severity of NAFLD. A panel of seven genetically diverse strains of inbred male mice (A/J, C57BL/6J, C3H/HeJ, 129S/SvImJ, CAST/EiJ, PWK/PhJ, and WSB/EiJ) were fed a choline- and folate-deficient (CFD) diet for 12 weeks. This diet induced liver injury in all mouse strains; however, the extent of NAFLD-associated pathomorphological changes in the livers was strain-specific, with A/J, C57BL/6J, and C3H/HeJ mice being the least sensitive and WSB/EiJ mice being the most sensitive. The morphological changes in the livers were accompanied by differences in the levels of hepatic and plasma miRNAs. The levels of circulating miR-34a, miR-122, miR-181a, miR-192, and miR-200b miRNAs were significantly correlated with a severity of NAFLD-specific liver pathomorphological features, with the strongest correlation occurring with miR-34a. These observations suggest that the plasma levels of miRNAs may be used as biomarkers for noninvasive monitoring the extent of NAFLD-associated liver injury and susceptibility to NAFLD. -- Highlights: ► Choline- and folate-deficiency induces a strain-specific fatty liver injury in mice. ► The extent of liver pathology was accompanied by the changes in microRNA expression. ► The levels of circulating microRNAs mirror the magnitude of fatty liver injury. ► Plasma microRNAs may be sensitive noninvasive indicators of the fatty liver injury.},
doi = {10.1016/J.TAAP.2012.04.018},
journal = {Toxicology and Applied Pharmacology},
issn = {0041-008X},
number = 1,
volume = 262,
place = {United States},
year = {2012},
month = {7}
}