Pancreatic Ubap2 deletion regulates glucose tolerance, inflammation, and protection from cerulein-induced pancreatitis.

Autor: Roy RV; Peggy and Charles Stephenson Cancer Center, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA; Department of Pathology, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA., Means N; Peggy and Charles Stephenson Cancer Center, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA; Department of Pathology, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA., Rao G; Peggy and Charles Stephenson Cancer Center, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA; Department of Pathology, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA., Asfa S; Peggy and Charles Stephenson Cancer Center, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA., Madka V; Center for Cancer Prevention and Drug Development, Department of Medicine, Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA., Dey A; Peggy and Charles Stephenson Cancer Center, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA; Department of Pathology, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA., Zhang Y; Peggy and Charles Stephenson Cancer Center, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA; Department of Pathology, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA., Choudhury M; Peggy and Charles Stephenson Cancer Center, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA; Department of Pathology, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA., Fung KM; Department of Pathology, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA., Dhanasekaran DN; Peggy and Charles Stephenson Cancer Center, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA; Department of Cell Biology, University of Oklahoma Health Science Center, Oklahoma City, OK, USA., Friedman JE; Harold Hamm Diabetes Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA., Crawford HC; Department of Surgery, Henry Ford Pancreatic Cancer Center, Henry Ford Health System, Detroit, MI, USA., Rao CV; Center for Cancer Prevention and Drug Development, Department of Medicine, Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA., Bhattacharya R; Peggy and Charles Stephenson Cancer Center, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA; Department of Obstetrics and Gynecology, University of Oklahoma Health Science Center, Oklahoma City, OK, USA., Mukherjee P; Peggy and Charles Stephenson Cancer Center, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA; Department of Pathology, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA. Electronic address: Priyabrata-Mukherjee@ouhsc.edu.
Jazyk: angličtina
Zdroj: Cancer letters [Cancer Lett] 2023 Dec 01; Vol. 578, pp. 216455. Date of Electronic Publication: 2023 Oct 19.
DOI: 10.1016/j.canlet.2023.216455
Abstrakt: Ubiquitin-binding associated protein 2 (UBAP2) is reported to promote macropinocytosis and pancreatic adenocarcinoma (PDAC) growth, however, its role in normal pancreatic function remains unknown. We addressed this knowledge gap by generating UBAP2 knockout (U2KO) mice under a pancreas-specific Cre recombinase (Pdx1-Cre). Pancreatic architecture remained intact in U2KO animals, but they demonstrated slight glucose intolerance compared to controls. Upon cerulein challenge to induce pancreatitis, U2KO animals had reduced levels of several pancreatitis-relevant cytokines, amylase and lipase in the serum, reduced tissue damage, and lessened neutrophil infiltration into the pancreatic tissue. Mechanistically, cerulein-challenged U2KO animals revealed reduced NF-κB activation compared to controls. In vitro promoter binding studies confirmed the reduction of NF-κB binding to its target molecules supporting UBAP2 as a new regulator of inflammation in pancreatitis and may be exploited as a therapeutic target in future to inhibit pancreatitis.
Competing Interests: Declaration of competing interest None of the authors have any conflicts of interest to disclose.
(Copyright © 2023 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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