Show simple item record

dc.contributor.authorMomen-Heravi, Fatemeh
dc.contributor.authorSaha, Banishree
dc.contributor.authorKodys, Karen
dc.contributor.authorCatalano, Donna
dc.contributor.authorSatishchandran, Abhishek
dc.contributor.authorSzabo, Gyongyi
dc.date2022-08-11T08:09:43.000
dc.date.accessioned2022-08-23T16:40:53Z
dc.date.available2022-08-23T16:40:53Z
dc.date.issued2015-08-12
dc.date.submitted2015-09-04
dc.identifier.citationJ Transl Med. 2015 Aug 12;13:261. doi: 10.1186/s12967-015-0623-9. <a href="http://dx.doi.org/10.1186/s12967-015-0623-9">Link to article on publisher's site</a>
dc.identifier.issn1479-5876 (Linking)
dc.identifier.doi10.1186/s12967-015-0623-9
dc.identifier.pmid26264599
dc.identifier.urihttp://hdl.handle.net/20.500.14038/39773
dc.description.abstractBACKGROUND: It has been well documented that alcohol and its metabolites induce injury and inflammation in the liver. However, there is no potential biomarker to monitor the extent of liver injury in alcoholic hepatitis patients. MicroRNAs (miRNAs) are a class of non-coding RNAs that are involved in various physiologic and pathologic processes. In the circulation, a great proportion of miRNAs is associated with extracellular vesicles (EVs)/exosomes. Here, we hypothesized that the exosome-associated miRNAs can be used as potential biomarkers in alcoholic hepatitis (AH). METHODS: Exosomes were isolated from sera of alcohol-fed mice or pair-fed mice, and plasma of alcoholic hepatitis patients or healthy controls by ExoQuick. The exosomes were characterized by transmission electron microscopy and Western blot and enumerated with a Nanoparticle Tracking Analysis system. Firefly microRNA Assay was performed on miRNA extracted from mice sera. TaqMan microRNA assay was used to identify differentially expressed miRNAs in plasma of cohort of patients with AH versus controls followed by construction of receiver operating characteristic (ROC) curves to determine the sensitivity and specificity of the candidates. RESULTS: The total number of circulating EVs was significantly increased in mice after alcohol feeding. Those EVs mainly consisted of exosomes, the smaller size vesicle subpopulation of EVs. By performing microarray screening on exosomes, we found nine inflammatory miRNAs which were deregulated in sera of chronic alcohol-fed mice compared to controls including upregulated miRNAs: miRNA-192, miRNA-122, miRNA-30a, miRNA-744, miRNA-1246, miRNA 30b and miRNA-130a. The ROC analyses indicated excellent diagnostic value of miRNA-192, miRNA-122, and miRNA-30a to identify alcohol-induced liver injury. We further validated findings from our animal model in human samples. Consistent with the animal model, total number of EVs, mostly exosomes, was significantly increased in human subjects with AH. Both miRNA-192 and miRNA-30a were significantly increased in the circulation of subjects with AH. miRNA-192 showed promising value for the diagnosis of AH. CONCLUSION: Elevated level of EVs/exosomes and exosome-associated miRNA signature could serve as potential diagnostic markers for AH. In addition to the biomarker diagnostic capabilities, these findings may facilitate development of novel strategies for diagnostics, monitoring, and therapeutics of AH.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=26264599&dopt=Abstract">Link to Article in PubMed</a>
dc.rights<p>© 2015 Momen-Heravi et al. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons. org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.</p>
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectAcute alcoholic hepatitis
dc.subjectAlcohol
dc.subjectLiver injury
dc.subjectExtracellular vesicles
dc.subjectExosomes
dc.subjectMicrovesicles
dc.subjectBiomarker
dc.subjectLiquid biopsy
dc.subjectmiRNA
dc.subjectBiological Factors
dc.subjectCells
dc.subjectDigestive System Diseases
dc.subjectGastroenterology
dc.subjectGenetics and Genomics
dc.subjectHepatology
dc.subjectSubstance Abuse and Addiction
dc.subjectTranslational Medical Research
dc.titleIncreased number of circulating exosomes and their microRNA cargos are potential novel biomarkers in alcoholic hepatitis
dc.typeJournal Article
dc.source.journaltitleJournal of translational medicine
dc.source.volume13
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=3575&amp;context=oapubs&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/oapubs/2571
dc.identifier.contextkey7559987
refterms.dateFOA2022-08-23T16:40:54Z
html.description.abstract<p>BACKGROUND: It has been well documented that alcohol and its metabolites induce injury and inflammation in the liver. However, there is no potential biomarker to monitor the extent of liver injury in alcoholic hepatitis patients. MicroRNAs (miRNAs) are a class of non-coding RNAs that are involved in various physiologic and pathologic processes. In the circulation, a great proportion of miRNAs is associated with extracellular vesicles (EVs)/exosomes. Here, we hypothesized that the exosome-associated miRNAs can be used as potential biomarkers in alcoholic hepatitis (AH).</p> <p>METHODS: Exosomes were isolated from sera of alcohol-fed mice or pair-fed mice, and plasma of alcoholic hepatitis patients or healthy controls by ExoQuick. The exosomes were characterized by transmission electron microscopy and Western blot and enumerated with a Nanoparticle Tracking Analysis system. Firefly microRNA Assay was performed on miRNA extracted from mice sera. TaqMan microRNA assay was used to identify differentially expressed miRNAs in plasma of cohort of patients with AH versus controls followed by construction of receiver operating characteristic (ROC) curves to determine the sensitivity and specificity of the candidates.</p> <p>RESULTS: The total number of circulating EVs was significantly increased in mice after alcohol feeding. Those EVs mainly consisted of exosomes, the smaller size vesicle subpopulation of EVs. By performing microarray screening on exosomes, we found nine inflammatory miRNAs which were deregulated in sera of chronic alcohol-fed mice compared to controls including upregulated miRNAs: miRNA-192, miRNA-122, miRNA-30a, miRNA-744, miRNA-1246, miRNA 30b and miRNA-130a. The ROC analyses indicated excellent diagnostic value of miRNA-192, miRNA-122, and miRNA-30a to identify alcohol-induced liver injury. We further validated findings from our animal model in human samples. Consistent with the animal model, total number of EVs, mostly exosomes, was significantly increased in human subjects with AH. Both miRNA-192 and miRNA-30a were significantly increased in the circulation of subjects with AH. miRNA-192 showed promising value for the diagnosis of AH.</p> <p>CONCLUSION: Elevated level of EVs/exosomes and exosome-associated miRNA signature could serve as potential diagnostic markers for AH. In addition to the biomarker diagnostic capabilities, these findings may facilitate development of novel strategies for diagnostics, monitoring, and therapeutics of AH.</p>
dc.identifier.submissionpathoapubs/2571
dc.contributor.departmentDepartment of Medicine, Division of Gastroenterology
dc.source.pages261


Files in this item

Thumbnail
Name:
s12967_015_0623_9.pdf
Size:
2.184Mb
Format:
PDF

This item appears in the following Collection(s)

Show simple item record

<p>© 2015 Momen-Heravi et al. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons. org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.</p>
Except where otherwise noted, this item's license is described as <p>© 2015 Momen-Heravi et al. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons. org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.</p>