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dc.contributor.authorTsay, Hsin-Chieh
dc.contributor.authorYuan, Qinggong
dc.contributor.authorBalakrishnan, Asha
dc.contributor.authorKaiser, Marina
dc.contributor.authorMöbus, Selina
dc.contributor.authorKozdrowska, Emilia
dc.contributor.authorFarid, Marwa
dc.contributor.authorTegtmeyer, Pia-Katharina
dc.contributor.authorBorst, Katharina
dc.contributor.authorVondran, Florian W R
dc.contributor.authorKalinke, Ulrich
dc.contributor.authorKispert, Andreas
dc.contributor.authorManns, Michael P
dc.contributor.authorOtt, Michael
dc.contributor.authorSharma, Amar Deep
dc.date.accessioned2019-03-01T12:37:57Z
dc.date.available2019-03-01T12:37:57Z
dc.date.issued2018-12-22
dc.identifier.issn1600-0641
dc.identifier.pmid30582979
dc.identifier.doi10.1016/j.jhep.2018.12.016
dc.identifier.urihttp://hdl.handle.net/10033/621708
dc.description.abstractFibrosis, a cardinal feature of a dysfunctional liver, significantly contributes to the ever-increasing mortality due to end-stage chronic liver diseases. The crosstalk between hepatocytes and hepatic stellate cells (HSCs) plays a key role in the progression of fibrosis. Although ample efforts have been devoted to elucidate the functions of HSCs during liver fibrosis, the regulatory functions of hepatocytes remain elusive. Using an unbiased functional microRNA (miRNA) screening, we investigated the ability of hepatocytes to regulate fibrosis by fine-tuning gene expression via miRNA modulation. The in vivo functional analyses were performed by inhibiting miRNA in hepatocytes using adeno-associated virus in carbon-tetrachloride- and 3,5-di-diethoxycarbonyl-1,4-dihydrocollidine-induced liver fibrosis. Blocking miRNA-221-3p function in hepatocytes during chronic liver injury facilitated recovery of the liver and faster resolution of the deposited extracellular matrix. Furthermore, we demonstrate that reduced secretion of C-C motif chemokine ligand 2, as a result of post-transcriptional regulation of GNAI2 (G protein alpha inhibiting activity polypeptide 2) by miRNA-221-3p, mitigates liver fibrosis. Collectively, miRNA modulation in hepatocytes, an easy-to-target cell type in the liver, may serve as a potential therapeutic approach for liver fibrosis.en_US
dc.publisherElsevieren_US
dc.rightsAttribution-NonCommercial-ShareAlike 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.subjectChemokine ligandsen_US
dc.subjectFibrosisen_US
dc.subjectHepatic stellate cellsen_US
dc.subjectmiRNAen_US
dc.subjectmiRNA-221-3pen_US
dc.titleHepatocyte-specific suppression of microRNA-221-3p mitigates liver fibrosis.en_US
dc.typeArticleen_US
dc.contributor.departmentHZI, Helmholtz Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig Germany.en_US
dc.identifier.journalJournal of Hepatologyen_US
dc.source.journaltitleJournal of hepatology


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