Utilize este identificador para referenciar este registo: http://hdl.handle.net/10400.7/895
Título: Dipeptidyl Peptidase-4 Is a Pro-Recovery Mediator During Acute Hepatotoxic Damage and Mirrors Severe Shifts in Kupffer Cells
Autor: Duarte, Nádia
Coelho, Inês
Holovanchuk, Denys
Inês Almeida, Joana
Penha-Gonçalves, Carlos
Paula Macedo, Maria
Palavras-chave: Dipeptidyl Peptidase‐4
Hepatotoxic
Kupffer Cells
CD26/DPP-4
Data: 7-Set-2018
Citação: 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
Resumo: 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.
Descrição: This deposit is composed by the main article plus the supplementary materials of the publication.
Peer review: yes
URI: http://hdl.handle.net/10400.7/895
DOI: 10.1002/hep4.1225
Versão do Editor: https://aasldpubs.onlinelibrary.wiley.com/doi/abs/10.1002/hep4.1225
Aparece nas colecções:DG - Artigos em revistas científicas

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Duarte_et_al_Hepatology_Communications_(2018).pdfmain article1,13 MBAdobe PDFVer/Abrir
Duarte_et_al_Hepatology_Communications_(2018)_SM.pdfsupplementary materials1,45 MBAdobe PDFVer/Abrir


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