Journal article
The pro-fibrotic role of dipeptidyl peptidase 4 in carbon tetrachloride-induced experimental liver injury
XM Wang, LE Holz, S Chowdhury, SP Cordoba, KA Evans, MG Gall, AJV De Ribeiro, YZ Zheng, MT Levy, DMT Yu, TW Yao, N Polak, CJ Jolly, P Bertolino, GW McCaughan, MD Gorrell
Immunology and Cell Biology | NATURE PUBLISHING GROUP | Published : 2017
DOI: 10.1038/icb.2016.116
Abstract
Liver fibrosis is a progressive pathological process involving inflammation and extracellular matrix deposition. Dipeptidyl peptidase 4 (DPP4), also known as CD26, is a cell surface glycoprotein and serine protease. DPP4 binds to fibronectin, can inactivate specific chemokines, incretin hormone and neuropeptides, and influences cell adhesion and migration. Such properties suggest a pro-fibrotic role for this peptidase but this hypothesis needs in vivo examination. Experimental liver injury was induced with carbon tetrachloride (CCl 4) in DPP4 gene knockout (gko) mice. DPP4 gko had less liver fibrosis and inflammation and fewer B cell clusters than wild type mice in the fibrosis model. DPP4 i..
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Awarded by National Health and Medical Research Council (NHMRC) of Australia
Awarded by NHMRC
Awarded by National Health and Medical Research Council of Australia
Funding Acknowledgements
We thank Dr Didier Marguet of Centre d'Immunologie de Marseille Luminy for the DPP4 gko mice and Dr Volker Benseler for confocal images. MK-0626 was provided in kind by the Investigator-Initiated Studies Program of Merck Sharp & Dohme Corporation. The opinions expressed in this paper are those of the authors and do not necessarily represent those of Merck Sharp & Dohme. National Health and Medical Research Council (NHMRC) of Australia project grants 293803, 512282 and 1105238 to MDG and GWM, NHMRC program grant 358398 (GWM), a Diabetes Australia grant to MDG and NHMRC Postgraduate Scholarships to XMW and MTL supported this work. TWY, LH and YZZ each received an Australian Postgraduate Award. MGG received a Sydney Medical School Foundation Francis M. Hooper Postgraduate Award.