Show simple item record

dc.contributor.authorYang, Dakai
dc.contributor.authorYuan, Qinggong
dc.contributor.authorBalakrishnan, Asha
dc.contributor.authorBantel, Heike
dc.contributor.authorKlusmann, Jan-Henning
dc.contributor.authorManns, Michael P
dc.contributor.authorOtt, Michael
dc.contributor.authorCantz, Tobias
dc.contributor.authorSharma, Amar Deep
dc.date.accessioned2016-09-08T09:45:44Z
dc.date.available2016-09-08T09:45:44Z
dc.date.issued2016
dc.identifier.citationMicroRNA-125b-5p mimic inhibits acute liver failure. 2016, 7:11916 Nat Communen
dc.identifier.issn2041-1723
dc.identifier.pmid27336362
dc.identifier.doi10.1038/ncomms11916
dc.identifier.urihttp://hdl.handle.net/10033/619994
dc.description.abstractThe lack of broad-spectrum anti-acute liver failure (ALF) therapeutic agents contributes to ALF-related mortality. MicroRNAs (miRNAs) are suggested to be potent serum biomarkers for ALF, but their functional and therapeutic relevance in ALF are unclear. Here we show an unbiased approach, using two complementary miRNA screens, to identify miRNAs that can attenuate ALF. We identify miR-125b-5p as a regulator of cell death that attenuates paracetamol-induced and FAS-induced toxicity in mouse and human hepatocytes. Importantly, administration of miR-125b-5p mimic in mouse liver prevents injury and improves survival in models of ALF. Functional studies show that miR-125b-5p ameliorates ALF by directly regulating kelch-like ECH-associated protein 1, in turn elevating expression of nuclear factor-E2-related factor 2, a known regulator in ALF. Collectively, our findings establish miR-125b-5p as an important regulator of paracetamol-induced and FAS-induced cell death. Thus, miR-125b-5p mimic may serve as a broad-spectrum therapeutic attenuator of cell death during ALF.
dc.language.isoenen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.titleMicroRNA-125b-5p mimic inhibits acute liver failure.en
dc.typeArticleen
dc.contributor.departmentTwincore Centre of Experimental and Clinical Infection Research; a joint venture between the Hannover Medical School and the Helmholtz Centre for Infection Research, Hannover 30625, Germany.en
dc.identifier.journalNature communicationsen
refterms.dateFOA2018-06-12T16:58:14Z
html.description.abstractThe lack of broad-spectrum anti-acute liver failure (ALF) therapeutic agents contributes to ALF-related mortality. MicroRNAs (miRNAs) are suggested to be potent serum biomarkers for ALF, but their functional and therapeutic relevance in ALF are unclear. Here we show an unbiased approach, using two complementary miRNA screens, to identify miRNAs that can attenuate ALF. We identify miR-125b-5p as a regulator of cell death that attenuates paracetamol-induced and FAS-induced toxicity in mouse and human hepatocytes. Importantly, administration of miR-125b-5p mimic in mouse liver prevents injury and improves survival in models of ALF. Functional studies show that miR-125b-5p ameliorates ALF by directly regulating kelch-like ECH-associated protein 1, in turn elevating expression of nuclear factor-E2-related factor 2, a known regulator in ALF. Collectively, our findings establish miR-125b-5p as an important regulator of paracetamol-induced and FAS-induced cell death. Thus, miR-125b-5p mimic may serve as a broad-spectrum therapeutic attenuator of cell death during ALF.


Files in this item

Thumbnail
Name:
Yang et al.pdf
Size:
1.767Mb
Format:
PDF
Description:
Open Access publication

This item appears in the following Collection(s)

Show simple item record

http://creativecommons.org/licenses/by-nc-sa/4.0/
Except where otherwise noted, this item's license is described as http://creativecommons.org/licenses/by-nc-sa/4.0/