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dc.contributor.authorYang, Dakai
dc.contributor.authorDai, Zhen
dc.contributor.authorYang, Taihua
dc.contributor.authorBalakrishnan, Asha
dc.contributor.authorYuan, Qinggong
dc.contributor.authorVondran, Florian W R
dc.contributor.authorManns, Michael P
dc.contributor.authorOtt, Michael
dc.contributor.authorCantz, Tobias
dc.contributor.authorSharma, Amar Deep
dc.date.accessioned2021-09-16T13:09:25Z
dc.date.available2021-09-16T13:09:25Z
dc.date.issued2020-09-15
dc.identifier.citationHepatol Commun. 2020 Sep 15;4(12):1851-1863. doi: 10.1002/hep4.1597.en_US
dc.identifier.pmid33305155
dc.identifier.doi10.1002/hep4.1597
dc.identifier.urihttp://hdl.handle.net/10033/623035
dc.description.abstractThe ability of the liver to regenerate and restore mass limits the increasing mortality rate due to life-threatening liver diseases. Successful liver regeneration is accomplished in multiple stages, of which the priming and proliferation phases are well studied. However, the regulatory pathways, specifically microRNA (miRNA)-mediated posttranscriptional regulation, which prevent uncontrolled proliferation and mediate the termination of liver regeneration, are not well understood. We identified differentially regulated miRNAs during the termination phase after 2/3 partial hepatectomy (PH) in mice, which is a well-established mouse model of liver regeneration. We further evaluated the function of differentially regulated miRNAs in primary mouse hepatocytes by using mimics and inhibitors and in vivo by using adeno-associated virus (AAV) serotype 8. A candidate miRNA target was identified by messenger RNA array in silico analyses and validated in primary mouse and human hepatocytes. Using miRNA profiling, we discovered miR-125b-5p as a novel regulator of hepatocyte proliferation in the late phase of liver regeneration. AAV-mediated miR-125b-5p delivery in mice enhanced the endogenous regenerative capacity and resulted in improved restoration of liver mass after 2/3 PH. Further, we found that ankyrin repeat and BTB/POZ domain containing protein 1 (Abtb1) is a direct target of miR-125b-5p in primary mouse and human hepatocytes and contributes to the pro-proliferative activity of miR-125b-5p by forkhead box G1 (FOXG1) and the cyclin-dependent kinase inhibitor 1A (p21) pathway. Conclusion: miR-125b-5p has an important role in regulating hepatocyte proliferation in the termination phase of liver regeneration and may serve as a potential therapeutic target in various liver diseases that often exhibit deregulated hepatocyte proliferation.en_US
dc.language.isoenen_US
dc.publisherWileyen_US
dc.rightsAttribution 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.titleMicroRNA-125b-5p Regulates Hepatocyte Proliferation During the Termination Phase of Liver Regeneration.en_US
dc.typeArticleen_US
dc.identifier.eissn2471-254X
dc.contributor.departmentTWINCORE, Zentrum für experimentelle und klinische Infektionsforschung GmbH,Feodor-Lynen Str. 7, 30625 Hannover, Germany.en_US
dc.identifier.journalHepatology communicationsen_US
dc.source.volume4
dc.source.issue12
dc.source.beginpage1851
dc.source.endpage1863
refterms.dateFOA2021-09-16T13:09:26Z
dc.source.journaltitleHepatology communications
dc.source.countryUnited States


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Except where otherwise noted, this item's license is described as Attribution 4.0 International