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Reduction in O-GlcNAcylation Mitigates the Severity of Inflammatory Response in Cerulein-Induced Acute Pancreatitis in a Mouse Model. | LitMetric

AI Article Synopsis

Article Abstract

Acute pancreatitis (AP) involves premature trypsinogen activation, which mediates a cascade of pro-inflammatory signaling that causes early stages of pancreatic injury. Activation of the transcription factor κB (NF-κB) and secretion of pro-inflammatory mediators are major events in AP. O-GlcNAc transferase (OGT), a stress-sensitive enzyme, was recently implicated to regulate NF-κB activation and inflammation in AP in vitro. This study aims to determine whether a pancreas-specific transgenic reduction in OGT in a mouse model affects the severity of AP in vivo. Mice with reduced pancreatic OGT (OGT) at 8 weeks of age were randomized to cerulein, which induces pancreatitis, or saline injections. AP was confirmed by elevated amylase levels and on histological analysis. The histological scoring demonstrated that OGT mice had decreased severity of AP. Additionally, serum lipase, LDH, and TNF-α in OGT did not significantly increase in response to cerulein treatment as compared to controls, suggesting attenuated AP induction in this model. Our study reveals the effect of reducing pancreatic OGT levels on the severity of pancreatitis, warranting further investigation on the role of OGT in the pathology of AP.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8945657PMC
http://dx.doi.org/10.3390/biology11030347DOI Listing

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