Pancreatic Ubap2 deletion regulates glucose tolerance, inflammation, and protection from cerulein-induced pancreatitis
Recommended Citation
Roy RV, Means N, Rao G, Asfa S, Madka V, Dey A, Zhang Y, Choudhury M, Fung KM, Dhanasekaran DN, Friedman JE, Crawford HC, Rao CV, Bhattacharya R, and Mukherjee P. Pancreatic Ubap2 deletion regulates glucose tolerance, inflammation, and protection from cerulein-induced pancreatitis. Cancer Lett 2023; 578:216455.
Document Type
Article
Publication Date
12-1-2023
Publication Title
Cancer letters
Abstract
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.
Medical Subject Headings
Mice; Animals; Ceruletide; NF-kappa B; Adenocarcinoma; Pancreatic Neoplasms; Pancreatitis; Pancreas; Inflammation; Glucose; Acute Disease
PubMed ID
37865160
Volume
578
First Page
216455
Last Page
216455
