Utilize este identificador para referenciar este registo: http://hdl.handle.net/10400.7/895
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dc.contributor.authorDuarte, Nádia-
dc.contributor.authorCoelho, Inês-
dc.contributor.authorHolovanchuk, Denys-
dc.contributor.authorInês Almeida, Joana-
dc.contributor.authorPenha-Gonçalves, Carlos-
dc.contributor.authorPaula Macedo, Maria-
dc.date.accessioned2018-09-25T13:30:13Z-
dc.date.available2018-09-25T13:30:13Z-
dc.date.issued2018-09-07-
dc.identifier.citationDuarte, N. , Coelho, I. , Holovanchuk, D. , Inês Almeida, J. , Penha‐Gonçalves, C. and Paula Macedo, M. (2018), Dipeptidyl Peptidase‐4 Is a Pro‐Recovery Mediator During Acute Hepatotoxic Damage and Mirrors Severe Shifts in Kupffer Cells. Hepatology Communications, 2: 1080-1094. doi:10.1002/hep4.1225pt_PT
dc.identifier.urihttp://hdl.handle.net/10400.7/895-
dc.descriptionThis deposit is composed by the main article plus the supplementary materials of the publication.pt_PT
dc.description.abstractDipeptidyl peptidase-4 (DPP-4 or clusters of differentiation [CD]26) is a multifunctional molecule with established roles in metabolism. Pharmacologic inhibition of DPP-4 is widely used to improve glycemic control through regulation of the incretin effect. Colaterally, CD26/DPP-4 inhibition appears to be beneficial in many inflammatory conditions, namely in delaying progression of liver pathology. Nevertheless, the exact implications of CD26/DPP-4 enzymatic activity in liver dysfunction remain unclear. In this work, we investigated the involvement of CD26/DPP-4 in experimental mouse models of induced hepatocyte damage that severely impact Kupffer cell (KC) populations. Liver dysfunction was evaluated in CD26 knockout (KO) and B6 wild-type mice during acute liver damage induced by acetaminophen, chronic liver damage induced by carbon tetrachloride, and KC-depleting treatment with clodronate-loaded liposomes. We found that necrosis resolution after hepatotoxic injury was delayed in CD26KO mice and in B6 mice treated with the CD26/DPP-4 inhibitor sitagliptin, suggesting that DPP-4 enzymatic activity plays a role in recovering from acute liver damage. Interestingly, the severe KC population reduction in acute and chronic liver injury was concomitant with increased CD26/DPP-4 serum levels. Remarkably, both chronic liver damage and noninflammatory depletion of KCs by clodronate liposomes were marked by oscillation in CD26/DPP-4 serum activity that mirrored the kinetics of liver KC depletion/recovery. Conclusion:CD26/DPP-4 enzymatic activity contributes to necrosis resolution during recovery from acute liver injury. Serum CD26/DPP-4 is elevated when severe perturbations are imposed on KC populations, regardless of patent liver damage. We propose that serum CD26/DPP-4 is a potential systemic surrogate marker of severe impairments in the KC population imposed by clinical and subclinical liver conditions.pt_PT
dc.description.sponsorshipFundingSupported by the Fundação para a Ciência e Tecnologia (grant no. PTDC/BIM‐MET/0486/2012), iNOVA4Health (UID/Multi/04462/2013), the European Commission Marie Skłodowska‐Curie Actions H2020 (grant agreements no. 722619 and no. 734719), the Sociedade Portuguesa de Diabetologia Bolsa Charneco da Costa 2017, and a Fundação para a Ciência e Tecnologia fellowship no. PD/BD/105997/2014 to I.C.pt_PT
dc.language.isoengpt_PT
dc.relationinfo:eu-repo/grantAgreement/EC/H2020/722619/EUpt_PT
dc.relationinfo:eu-repo/grantAgreement/EC/H2020/734719/EUpt_PT
dc.relationPD/BD/105997/2014pt_PT
dc.relationinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/124913/PTpt_PT
dc.relationinfo:eu-repo/grantAgreement/FCT/5876/147260/PTpt_PT
dc.rightsopenAccesspt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectDipeptidyl Peptidase‐4pt_PT
dc.subjectHepatotoxicpt_PT
dc.subjectKupffer Cellspt_PT
dc.subjectCD26/DPP-4pt_PT
dc.titleDipeptidyl Peptidase-4 Is a Pro-Recovery Mediator During Acute Hepatotoxic Damage and Mirrors Severe Shifts in Kupffer Cellspt_PT
dc.typearticlept_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
degois.publication.firstPage1080pt_PT
degois.publication.issue9pt_PT
degois.publication.lastPage1094pt_PT
degois.publication.titleHepatology Communicationspt_PT
dc.relation.publisherversionhttps://aasldpubs.onlinelibrary.wiley.com/doi/abs/10.1002/hep4.1225pt_PT
dc.peerreviewedyespt_PT
degois.publication.volume2pt_PT
dc.identifier.doi10.1002/hep4.1225pt_PT
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Duarte_et_al_Hepatology_Communications_(2018)_SM.pdfsupplementary materials1,45 MBAdobe PDFVer/Abrir


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