{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,7,2]],"date-time":"2024-07-02T04:31:38Z","timestamp":1719894698358},"reference-count":30,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"9","license":[{"start":{"date-parts":[[2018,9,1]],"date-time":"2018-09-01T00:00:00Z","timestamp":1535760000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"award":["Grant Agreement N\u00ba 722619","Grant Agreement N\u00ba 734719"],"award-info":[{"award-number":["Grant Agreement N\u00ba 722619","Grant Agreement N\u00ba 734719"]}]},{"award":["PD\/BD\/105997\/2014","PTDC\/BIM-MET\/0486\/2012","iNOVA4Health \u2013 UID\/Multi\/04462\/2013"],"award-info":[{"award-number":["PD\/BD\/105997\/2014","PTDC\/BIM-MET\/0486\/2012","iNOVA4Health \u2013 UID\/Multi\/04462\/2013"]}]},{"award":["722619","734719"],"award-info":[{"award-number":["722619","734719"]}]},{}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Hepatology Communications"],"published-print":{"date-parts":[[2018,9]]},"abstract":"<jats:p>Dipeptidyl peptidase\u20104 (DPP\u20104 or clusters of differentiation [CD]26) is a multifunctional molecule with established roles in metabolism. Pharmacologic inhibition of DPP\u20104 is widely used to improve glycemic control through regulation of the incretin effect. Colaterally, CD26\/DPP\u20104 inhibition appears to be beneficial in many inflammatory conditions, namely in delaying progression of liver pathology. Nevertheless, the exact implications of CD26\/DPP\u20104 enzymatic activity in liver dysfunction remain unclear. In this work, we investigated the involvement of CD26\/DPP\u20104 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\u2010type mice during acute liver damage induced by acetaminophen, chronic liver damage induced by carbon tetrachloride, and KC\u2010depleting treatment with clodronate\u2010loaded liposomes. We found that necrosis resolution after hepatotoxic injury was delayed in CD26KO mice and in B6 mice treated with the CD26\/DPP\u20104 inhibitor sitagliptin, suggesting that DPP\u20104 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\u20104 serum levels. Remarkably, both chronic liver damage and noninflammatory depletion of KCs by clodronate liposomes were marked by oscillation in CD26\/DPP\u20104 serum activity that mirrored the kinetics of liver KC depletion\/recovery. <jats:italic toggle=\"yes\">Conclusion<\/jats:italic>:CD26\/DPP\u20104 enzymatic activity contributes to necrosis resolution during recovery from acute liver injury. Serum CD26\/DPP\u20104 is elevated when severe perturbations are imposed on KC populations, regardless of patent liver damage. We propose that serum CD26\/DPP\u20104 is a potential systemic surrogate marker of severe impairments in the KC population imposed by clinical and subclinical liver conditions.<\/jats:p>","DOI":"10.1002\/hep4.1225","type":"journal-article","created":{"date-parts":[[2018,9,7]],"date-time":"2018-09-07T15:27:36Z","timestamp":1536334056000},"page":"1080-1094","source":"Crossref","is-referenced-by-count":10,"title":["Dipeptidyl Peptidase\u20104 Is a Pro\u2010Recovery Mediator During Acute Hepatotoxic Damage and Mirrors Severe Shifts in Kupffer Cells"],"prefix":"10.1097","volume":"2","author":[{"given":"N\u00e1dia","family":"Duarte","sequence":"first","affiliation":[{"name":"Instituto Gulbenkian de Ci\u00eancia,Oeiras,Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"In\u00eas","family":"Coelho","sequence":"additional","affiliation":[{"name":"Instituto Gulbenkian de 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