2.50
Hdl Handle:
http://hdl.handle.net/10033/619994
Title:
MicroRNA-125b-5p mimic inhibits acute liver failure.
Authors:
Yang, Dakai; Yuan, Qinggong; Balakrishnan, Asha; Bantel, Heike; Klusmann, Jan-Henning; Manns, Michael P; Ott, Michael; Cantz, Tobias; Sharma, Amar Deep
Abstract:
The 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.
Affiliation:
Twincore 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.
Citation:
MicroRNA-125b-5p mimic inhibits acute liver failure. 2016, 7:11916 Nat Commun
Journal:
Nature communications
Issue Date:
2016
URI:
http://hdl.handle.net/10033/619994
DOI:
10.1038/ncomms11916
PubMed ID:
27336362
Type:
Article
Language:
en
ISSN:
2041-1723
Appears in Collections:
publications of the AG cell and gene therapy

Full metadata record

DC FieldValue Language
dc.contributor.authorYang, Dakaien
dc.contributor.authorYuan, Qinggongen
dc.contributor.authorBalakrishnan, Ashaen
dc.contributor.authorBantel, Heikeen
dc.contributor.authorKlusmann, Jan-Henningen
dc.contributor.authorManns, Michael Pen
dc.contributor.authorOtt, Michaelen
dc.contributor.authorCantz, Tobiasen
dc.contributor.authorSharma, Amar Deepen
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.en
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

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