Version 1
: Received: 28 March 2024 / Approved: 29 March 2024 / Online: 29 March 2024 (08:34:13 CET)
How to cite:
Huang, J. C.; Tong, X. L.; Xiang, M. S. W.; Boumelhem, B. B.; Foulis, D. P.; Zhang, M.; McKenzie, C.; McCaughan, G. W.; Reinheckel, T.; Zhang, H. E.; Gorrell, M. D. Dipeptidyl Peptidase 9 (DPP9) Depletion From Hepatocytes in Mice Retards Liver Tumour Growth and Increases Intrahepatic Caspase-1 Activation. Preprints2024, 2024031824. https://doi.org/10.20944/preprints202403.1824.v1
Huang, J. C.; Tong, X. L.; Xiang, M. S. W.; Boumelhem, B. B.; Foulis, D. P.; Zhang, M.; McKenzie, C.; McCaughan, G. W.; Reinheckel, T.; Zhang, H. E.; Gorrell, M. D. Dipeptidyl Peptidase 9 (DPP9) Depletion From Hepatocytes in Mice Retards Liver Tumour Growth and Increases Intrahepatic Caspase-1 Activation. Preprints 2024, 2024031824. https://doi.org/10.20944/preprints202403.1824.v1
Huang, J. C.; Tong, X. L.; Xiang, M. S. W.; Boumelhem, B. B.; Foulis, D. P.; Zhang, M.; McKenzie, C.; McCaughan, G. W.; Reinheckel, T.; Zhang, H. E.; Gorrell, M. D. Dipeptidyl Peptidase 9 (DPP9) Depletion From Hepatocytes in Mice Retards Liver Tumour Growth and Increases Intrahepatic Caspase-1 Activation. Preprints2024, 2024031824. https://doi.org/10.20944/preprints202403.1824.v1
APA Style
Huang, J. C., Tong, X. L., Xiang, M. S. W., Boumelhem, B. B., Foulis, D. P., Zhang, M., McKenzie, C., McCaughan, G. W., Reinheckel, T., Zhang, H. E., & Gorrell, M. D. (2024). Dipeptidyl Peptidase 9 (DPP9) Depletion From Hepatocytes in Mice Retards Liver Tumour Growth and Increases Intrahepatic Caspase-1 Activation. Preprints. https://doi.org/10.20944/preprints202403.1824.v1
Chicago/Turabian Style
Huang, J. C., Hui Emma Zhang and Mark Douglas Gorrell. 2024 "Dipeptidyl Peptidase 9 (DPP9) Depletion From Hepatocytes in Mice Retards Liver Tumour Growth and Increases Intrahepatic Caspase-1 Activation" Preprints. https://doi.org/10.20944/preprints202403.1824.v1
Abstract
Dipeptidyl peptidase 9 (DPP9) is a multifunctional intracellular protease with roles in tumour growth, inflammation and mitochondrial function. We developed a hepatocyte-specific DPP9 knockout mouse (DPP9-KO) to explore DPP9 in a mouse model of hepatocellular carcinoma (HCC). DPP9-KO mice were generated by crossing Albumin-Cre mice (Wt/Wt Cre+/+) with DPP9 floxed mice (Fl/Fl Cre-/-). Mice were treated with Diethylnitrosamine and Thioacetamide then an atherogenic High Fat Diet until 28 weeks of age. DPP9-KO mice had reduced liver and subcuta-neous adipose tissue mass and lower fasting plasma glucose, fewer small macroscopic liver nod-ules compared to DPP9-WT mice. However, there were no differences in the total number of mac-roscopic liver nodules, tumour burden, inflammation score and steatosis score. Consistent with the known ability of DPP9 to suppress NLRP1 activation, activated caspase-1 protein was ele-vated in DPP9-KO mouse liver. Additionally, Nfkbib, Cxcl10 and Ccl5 mRNA and protein levels of autophagy marker beclin1 and tumour suppressor p53 were increased. In conclusion, DPP9 de-pletion in hepatocytes may reduce liver cancer initiation, via mechanisms that may include in-creased autophagy and innate tumour suppression in this experimental model. Finally, the data supports DPP9 having a role in glucose regulation by the liver.
Medicine and Pharmacology, Oncology and Oncogenics
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