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• W2891178306 endingPage "1094" @default.
• W2891178306 startingPage "1080" @default.
• W2891178306 abstract "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." @default.
• W2891178306 created "2018-09-27" @default.
• W2891178306 creator A5017125132 @default.
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• W2891178306 date "2018-09-01" @default.
• W2891178306 modified "2023-10-18" @default.
• W2891178306 title "Dipeptidyl Peptidase‐4 Is a Pro‐Recovery Mediator During Acute Hepatotoxic Damage and Mirrors Severe Shifts in Kupffer Cells" @default.
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• W2891178306 doi "https://doi.org/10.1002/hep4.1225" @default.
• W2891178306 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6128231" @default.
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• W2891178306 hasPublicationYear "2018" @default.
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