Dipeptidyl Peptidase-4 Is a Pro-Recovery Mediator During Acute Hepatotoxic Damage and Mirrors Severe Shifts in Kupffer Cells

Detalhes bibliográficos
Autor(a) principal: Duarte, Nádia
Data de Publicação: 2018
Outros Autores: Coelho, Inês, Holovanchuk, Denys, Inês Almeida, Joana, Penha-Gonçalves, Carlos, Paula Macedo, Maria
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10400.7/895
Resumo: This deposit is composed by the main article plus the supplementary materials of the publication.
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spelling Dipeptidyl Peptidase-4 Is a Pro-Recovery Mediator During Acute Hepatotoxic Damage and Mirrors Severe Shifts in Kupffer CellsDipeptidyl Peptidase‐4HepatotoxicKupffer CellsCD26/DPP-4This deposit is composed by the main article plus the supplementary materials of the publication.Dipeptidyl 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.FundingSupported 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.ARCADuarte, NádiaCoelho, InêsHolovanchuk, DenysInês Almeida, JoanaPenha-Gonçalves, CarlosPaula Macedo, Maria2018-09-25T13:30:13Z2018-09-072018-09-07T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfapplication/pdfhttp://hdl.handle.net/10400.7/895engDuarte, 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/hep4.122510.1002/hep4.1225info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2022-11-29T14:35:18Zoai:arca.igc.gulbenkian.pt:10400.7/895Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T16:12:06.216686Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Dipeptidyl Peptidase-4 Is a Pro-Recovery Mediator During Acute Hepatotoxic Damage and Mirrors Severe Shifts in Kupffer Cells
title Dipeptidyl Peptidase-4 Is a Pro-Recovery Mediator During Acute Hepatotoxic Damage and Mirrors Severe Shifts in Kupffer Cells
spellingShingle Dipeptidyl Peptidase-4 Is a Pro-Recovery Mediator During Acute Hepatotoxic Damage and Mirrors Severe Shifts in Kupffer Cells
Duarte, Nádia
Dipeptidyl Peptidase‐4
Hepatotoxic
Kupffer Cells
CD26/DPP-4
title_short Dipeptidyl Peptidase-4 Is a Pro-Recovery Mediator During Acute Hepatotoxic Damage and Mirrors Severe Shifts in Kupffer Cells
title_full Dipeptidyl Peptidase-4 Is a Pro-Recovery Mediator During Acute Hepatotoxic Damage and Mirrors Severe Shifts in Kupffer Cells
title_fullStr Dipeptidyl Peptidase-4 Is a Pro-Recovery Mediator During Acute Hepatotoxic Damage and Mirrors Severe Shifts in Kupffer Cells
title_full_unstemmed Dipeptidyl Peptidase-4 Is a Pro-Recovery Mediator During Acute Hepatotoxic Damage and Mirrors Severe Shifts in Kupffer Cells
title_sort Dipeptidyl Peptidase-4 Is a Pro-Recovery Mediator During Acute Hepatotoxic Damage and Mirrors Severe Shifts in Kupffer Cells
author Duarte, Nádia
author_facet Duarte, Nádia
Coelho, Inês
Holovanchuk, Denys
Inês Almeida, Joana
Penha-Gonçalves, Carlos
Paula Macedo, Maria
author_role author
author2 Coelho, Inês
Holovanchuk, Denys
Inês Almeida, Joana
Penha-Gonçalves, Carlos
Paula Macedo, Maria
author2_role author
author
author
author
author
dc.contributor.none.fl_str_mv ARCA
dc.contributor.author.fl_str_mv Duarte, Nádia
Coelho, Inês
Holovanchuk, Denys
Inês Almeida, Joana
Penha-Gonçalves, Carlos
Paula Macedo, Maria
dc.subject.por.fl_str_mv Dipeptidyl Peptidase‐4
Hepatotoxic
Kupffer Cells
CD26/DPP-4
topic Dipeptidyl Peptidase‐4
Hepatotoxic
Kupffer Cells
CD26/DPP-4
description This deposit is composed by the main article plus the supplementary materials of the publication.
publishDate 2018
dc.date.none.fl_str_mv 2018-09-25T13:30:13Z
2018-09-07
2018-09-07T00:00:00Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10400.7/895
url http://hdl.handle.net/10400.7/895
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Duarte, 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/hep4.1225
10.1002/hep4.1225
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
institution RCAAP
reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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