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miRNA-21 ablation protects against liver injury and necroptosis in cholestasis

2018-05Journal article Restricted access
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dc.contributor.authorAfonso, Marta B.
dc.contributor.authorRodrigues, Pedro M.
dc.contributor.authorSimão, André L.
dc.contributor.authorGaspar, Maria M.
dc.contributor.authorCarvalho, Tânia
dc.contributor.authorBorralho, Paula
dc.contributor.authorBañales, Jesús M.
dc.contributor.authorCastro, Rui E.
dc.contributor.authorRodrigues, Cecília M. P.
dc.date.accessioned2017-12-27T00:09:04Z
dc.date.available2017-12-27T00:09:04Z
dc.date.issued2018-05
dc.description.abstractInhibition of microRNA-21 (miR-21) prevents necroptosis in the mouse pancreas. Necroptosis contributes to hepatic necro-inflammation in the common bile duct ligation (BDL) murine model. We aimed to evaluate the role of miR-21 in mediating deleterious processes associated with cholestasis. Mechanistic studies established a functional link between miR-21 and necroptosis through cyclin-dependent kinase 2-associated protein 1 (CDK2AP1). miR-21 expression increased in the liver of primary biliary cholangitis (PBC) patients and BDL wild-type (WT) mice at both 3 and 14 days. Notably, under BDL, miR-21 -/- mice displayed decreased liver injury markers in serum compared with WT mice, accompanied by reduced hepatocellular degeneration, oxidative stress and fibrosis. Hallmarks of necroptosis were decreased in the liver of BDL miR-21 -/- mice, via relieved repression of CDK2AP1. Further, miR-21 -/- mice displayed improved adaptive response of bile acid homeostasis. In conclusion, miR-21 ablation ameliorates liver damage and necroptosis in BDL mice. Inhibition of miR-21 should arise as a promising approach to treat cholestasis.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationAfonso MB, Rodrigues PM, Simão AL, Gaspar MM, Carvalho T, Borralho P, et al. miRNA-21 ablation protects against liver injury and necroptosis in cholestasis. Cell Death Differentiation. 2018;25(5):857-72.pt_PT
dc.identifier.doi10.1038/s41418-017-0019-xpt_PT
dc.identifier.urihttp://hdl.handle.net/10400.21/7805
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherSpringer Publishing Companypt_PT
dc.relation.publisherversionhttps://www.nature.com/articles/s41418-017-0019-xpt_PT
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/pt_PT
dc.subjectCell deathpt_PT
dc.subjectImmune responsept_PT
dc.subjectGastrointestinal diseasept_PT
dc.titlemiRNA-21 ablation protects against liver injury and necroptosis in cholestasispt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage872pt_PT
oaire.citation.issue5pt_PT
oaire.citation.startPage857pt_PT
oaire.citation.titleCell Death & Differentiationpt_PT
oaire.citation.volume25pt_PT
rcaap.rightsrestrictedAccesspt_PT
rcaap.typearticlept_PT

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