The pro-fibrotic role of dipeptidyl peptidase 4 in carbon tetrachloride-induced experimental liver injury

The pro-fibrotic role of dipeptidyl peptidase 4 in carbon tetrachloride-induced experimental liver injury.

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Item Type: Article
Status: Published
Official URL: 10.1038/icb.2016.116
Journal or Publication Title: Immunology and Cell Biology
Volume: 95
Number: 5
Page Range: pp. 443-453
Date: May 2017
Divisions: Liver Enzymes in Metabolism and Inflammation
Liver Injury and Cancer
Depositing User: General Admin
Identification Number: 10.1038/icb.2016.116
Date Deposited: 16 Jun 2021 05:21
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 (CCl4) 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 inhibitor-treated mice also developed less liver fibrosis. DNA microarray and PCR showed that many immunoglobulin (Ig) genes and some metabolism-associated transcripts were differentially expressed in the gko strain compared with wild type. CCl4-treated DPP4 gko livers had more IgM+ and IgG+ intrahepatic lymphocytes, and fewer CD4+, IgD+ and CD21+ intrahepatic lymphocytes. These data suggest that DPP4 is pro-fibrotic in CCl4-induced liver fibrosis and that the mechanisms of DPP4 pro-fibrotic action include energy metabolism, B cells, NK cells and CD4+ cells.

Creators:
Creators
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Wang, Xin Maggie
UNSPECIFIED
Holz, Lauren E.
UNSPECIFIED
Chowdhury, Sumaiya
UNSPECIFIED
Cordoba, Shaun
UNSPECIFIED
Evans, Kathryn
UNSPECIFIED
Gall, Margaret G.
UNSPECIFIED
Vieira de Ribeiro, Ana Julia
UNSPECIFIED
Zheng, Yuan
UNSPECIFIED
Levy, Miriam
UNSPECIFIED
Yu, Denise
UNSPECIFIED
Yao, Tsun-Wen
UNSPECIFIED
Polak, Natasa
UNSPECIFIED
Bertolino, Patrick
UNSPECIFIED
Jolly, Christopher J.
UNSPECIFIED
McCaughan, Geoffrey W.
UNSPECIFIED
Gorrell, Mark D.
UNSPECIFIED
Last Modified: 16 Jun 2021 05:21
URI: https://eprints.centenary.org.au/id/eprint/1061

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