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
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...
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| Veröffentlicht in: | Toxicology and applied pharmacology 2012-07, Vol.262 (1), p.52-59 |
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| creator | Tryndyak, Volodymyr P. Latendresse, John R. Montgomery, Beverly Ross, Sharon A. Beland, Frederick A. Rusyn, Ivan Pogribny, Igor P. |
| description | 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 12weeks. 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.
► 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_str_mv | 10.1016/j.taap.2012.04.018 |
| format | Article |
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► 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.</description><identifier>ISSN: 0041-008X</identifier><identifier>EISSN: 1096-0333</identifier><identifier>DOI: 10.1016/j.taap.2012.04.018</identifier><identifier>PMID: 22561871</identifier><identifier>CODEN: TXAPA9</identifier><language>eng</language><publisher>Amsterdam: Elsevier Inc</publisher><subject>60 APPLIED LIFE SCIENCES ; ALANINES ; Animals ; Biological and medical sciences ; BIOLOGICAL MARKERS ; biomarkers ; Biomarkers - blood ; Blood ; CHOLINE ; Choline Deficiency - complications ; Diets ; Disease Models, Animal ; Fatty liver ; Fatty Liver - etiology ; Fatty Liver - genetics ; Fatty Liver - pathology ; Folic Acid Deficiency - complications ; Gastroenterology. Liver. Pancreas. Abdomen ; Genetic Predisposition to Disease ; Inbreeding ; INJURIES ; Inter-individual differences ; LACTATE DEHYDROGENASE ; LIVER ; Liver. Biliary tract. Portal circulation. Exocrine pancreas ; Male ; Medical sciences ; MICE ; Mice, Inbred C3H ; Mice, Inbred C57BL ; Mice, Inbred Strains ; microRNAs ; MicroRNAs - blood ; miRNA ; MORPHOLOGICAL CHANGES ; Mouse ; Non-alcoholic Fatty Liver Disease ; non-coding RNA ; Nonalcoholic fatty liver disease ; Noninvasive evaluation ; Other diseases. Semiology ; Plasma levels ; POLYMERASE CHAIN REACTION ; Severity of Illness Index ; Species Specificity ; Toxicology ; TRANSCRIPTION</subject><ispartof>Toxicology and applied pharmacology, 2012-07, Vol.262 (1), p.52-59</ispartof><rights>2012</rights><rights>2015 INIST-CNRS</rights><rights>Published by Elsevier Inc.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c546t-ea8ff3ae4e4b119b7b273b2138cb370fb41efaf1a1dab89f64cdf216e946bf213</citedby><cites>FETCH-LOGICAL-c546t-ea8ff3ae4e4b119b7b273b2138cb370fb41efaf1a1dab89f64cdf216e946bf213</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.taap.2012.04.018$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,780,784,885,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=26084846$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22561871$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://www.osti.gov/biblio/22215347$$D View this record in Osti.gov$$Hfree_for_read</backlink></links><search><creatorcontrib>Tryndyak, Volodymyr P.</creatorcontrib><creatorcontrib>Latendresse, John R.</creatorcontrib><creatorcontrib>Montgomery, Beverly</creatorcontrib><creatorcontrib>Ross, Sharon A.</creatorcontrib><creatorcontrib>Beland, Frederick A.</creatorcontrib><creatorcontrib>Rusyn, Ivan</creatorcontrib><creatorcontrib>Pogribny, Igor P.</creatorcontrib><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</title><title>Toxicology and applied pharmacology</title><addtitle>Toxicol Appl Pharmacol</addtitle><description>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 12weeks. 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.
► 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.</description><subject>60 APPLIED LIFE SCIENCES</subject><subject>ALANINES</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>BIOLOGICAL MARKERS</subject><subject>biomarkers</subject><subject>Biomarkers - blood</subject><subject>Blood</subject><subject>CHOLINE</subject><subject>Choline Deficiency - complications</subject><subject>Diets</subject><subject>Disease Models, Animal</subject><subject>Fatty liver</subject><subject>Fatty Liver - etiology</subject><subject>Fatty Liver - genetics</subject><subject>Fatty Liver - pathology</subject><subject>Folic Acid Deficiency - complications</subject><subject>Gastroenterology. Liver. Pancreas. Abdomen</subject><subject>Genetic Predisposition to Disease</subject><subject>Inbreeding</subject><subject>INJURIES</subject><subject>Inter-individual differences</subject><subject>LACTATE DEHYDROGENASE</subject><subject>LIVER</subject><subject>Liver. Biliary tract. Portal circulation. Exocrine pancreas</subject><subject>Male</subject><subject>Medical sciences</subject><subject>MICE</subject><subject>Mice, Inbred C3H</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Inbred Strains</subject><subject>microRNAs</subject><subject>MicroRNAs - blood</subject><subject>miRNA</subject><subject>MORPHOLOGICAL CHANGES</subject><subject>Mouse</subject><subject>Non-alcoholic Fatty Liver Disease</subject><subject>non-coding RNA</subject><subject>Nonalcoholic fatty liver disease</subject><subject>Noninvasive evaluation</subject><subject>Other diseases. Semiology</subject><subject>Plasma levels</subject><subject>POLYMERASE CHAIN REACTION</subject><subject>Severity of Illness Index</subject><subject>Species Specificity</subject><subject>Toxicology</subject><subject>TRANSCRIPTION</subject><issn>0041-008X</issn><issn>1096-0333</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kd-qEzEQxhdRPPXoC3ghARG82XWSTbe7IMLh4D84qIiCd2E2O7Ep26QmaaEP47ua0HrUG6-SML_vm5l8VfWYQ8OBdy82TULcNQK4aEA2wPs71YLD0NXQtu3dagEgeQ3Qf7uoHsS4AYBBSn6_uhBi2fF-xRfVz08zxi2yrdXBf_5wFRkGYpFctMkeiFk3WY3Jh8i8ya9EoY4poHVsssZQIKcp5gJL66I7ULDpWNg5y0MubPbhWGz2mqbC5U7ExiNDptd-to5qhm5ixs-YqJ7IWG3JpWxP6WF1z-Ac6dH5vKy-vnn95fpdffPx7fvrq5taL2WXasLemBZJkhw5H8bVKFbtKHjb67FdgRklJ4OGI59w7AfTST0ZwTsaZDfmS3tZvTr57vbjliad-wec1S7YLYaj8mjVvxVn1-q7Pygp-vzhkA2engx8TFZFbRPptfbOkU5KCMGXrVxl6vm5TfA_9hST2tqoaZ7Rkd9HxUH0IEBCMRQnNMcSYyBzOwwHVdJXG1XSVyV9BVLl9LPoyd9r3Ep-x52BZ2cAo8bZBHTaxj9cB73sZZe5lyeO8qcfLIWyUkl6sqFsNHn7vzl-AXoC0co</recordid><startdate>20120701</startdate><enddate>20120701</enddate><creator>Tryndyak, Volodymyr P.</creator><creator>Latendresse, John R.</creator><creator>Montgomery, Beverly</creator><creator>Ross, Sharon A.</creator><creator>Beland, Frederick A.</creator><creator>Rusyn, Ivan</creator><creator>Pogribny, Igor P.</creator><general>Elsevier Inc</general><general>Elsevier</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7U7</scope><scope>C1K</scope><scope>OTOTI</scope><scope>5PM</scope></search><sort><creationdate>20120701</creationdate><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</title><author>Tryndyak, Volodymyr P. ; Latendresse, John R. ; Montgomery, Beverly ; Ross, Sharon A. ; Beland, Frederick A. ; Rusyn, Ivan ; Pogribny, Igor P.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c546t-ea8ff3ae4e4b119b7b273b2138cb370fb41efaf1a1dab89f64cdf216e946bf213</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>60 APPLIED LIFE SCIENCES</topic><topic>ALANINES</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>BIOLOGICAL MARKERS</topic><topic>biomarkers</topic><topic>Biomarkers - blood</topic><topic>Blood</topic><topic>CHOLINE</topic><topic>Choline Deficiency - complications</topic><topic>Diets</topic><topic>Disease Models, Animal</topic><topic>Fatty liver</topic><topic>Fatty Liver - etiology</topic><topic>Fatty Liver - genetics</topic><topic>Fatty Liver - pathology</topic><topic>Folic Acid Deficiency - complications</topic><topic>Gastroenterology. Liver. Pancreas. Abdomen</topic><topic>Genetic Predisposition to Disease</topic><topic>Inbreeding</topic><topic>INJURIES</topic><topic>Inter-individual differences</topic><topic>LACTATE DEHYDROGENASE</topic><topic>LIVER</topic><topic>Liver. Biliary tract. Portal circulation. Exocrine pancreas</topic><topic>Male</topic><topic>Medical sciences</topic><topic>MICE</topic><topic>Mice, Inbred C3H</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Inbred Strains</topic><topic>microRNAs</topic><topic>MicroRNAs - blood</topic><topic>miRNA</topic><topic>MORPHOLOGICAL CHANGES</topic><topic>Mouse</topic><topic>Non-alcoholic Fatty Liver Disease</topic><topic>non-coding RNA</topic><topic>Nonalcoholic fatty liver disease</topic><topic>Noninvasive evaluation</topic><topic>Other diseases. 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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 12weeks. 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.
► 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.</abstract><cop>Amsterdam</cop><pub>Elsevier Inc</pub><pmid>22561871</pmid><doi>10.1016/j.taap.2012.04.018</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | 60 APPLIED LIFE SCIENCES ALANINES Animals Biological and medical sciences BIOLOGICAL MARKERS biomarkers Biomarkers - blood Blood CHOLINE Choline Deficiency - complications Diets Disease Models, Animal Fatty liver Fatty Liver - etiology Fatty Liver - genetics Fatty Liver - pathology Folic Acid Deficiency - complications Gastroenterology. Liver. Pancreas. Abdomen Genetic Predisposition to Disease Inbreeding INJURIES Inter-individual differences LACTATE DEHYDROGENASE LIVER Liver. Biliary tract. Portal circulation. Exocrine pancreas Male Medical sciences MICE Mice, Inbred C3H Mice, Inbred C57BL Mice, Inbred Strains microRNAs MicroRNAs - blood miRNA MORPHOLOGICAL CHANGES Mouse Non-alcoholic Fatty Liver Disease non-coding RNA Nonalcoholic fatty liver disease Noninvasive evaluation Other diseases. Semiology Plasma levels POLYMERASE CHAIN REACTION Severity of Illness Index Species Specificity Toxicology TRANSCRIPTION |
| 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 |
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