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

Journal Article · Sun Jul 01 04:00:00 EDT 2012 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/J.TAAP.2012.04.018· OSTI ID:22215347

Tryndyak, Volodymyr P. ^[1]; Latendresse, John R. ^[2]; Montgomery, Beverly ^[1]; Ross, Sharon A. ^[3]; Beland, Frederick A. ^[1]; Rusyn, Ivan ^[4]

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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)

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.

• OSTI ID: 22215347
• Journal Information: Toxicology and Applied Pharmacology, Journal Name: Toxicology and Applied Pharmacology Journal Issue: 1 Vol. 262; ISSN TXAPA9; ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ALANINES
BIOLOGICAL MARKERS
CHOLINE
INJURIES
LACTATE DEHYDROGENASE
LIVER
MICE
MORPHOLOGICAL CHANGES
POLYMERASE CHAIN REACTION
TRANSCRIPTION