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

Mackenzie Moore, Nandini Avula, Alicia Wong, Megan Beetch, Seokwon Jo, Emilyn U. Alejandro

Research output: Contribution to journalArticlepeer-review

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 (OGTPanc+/−) 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 OGTPanc+/− mice had decreased severity of AP. Additionally, serum lipase, LDH, and TNF-α in OGTPanc+/− 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.

Original languageEnglish (US)
Article number347
JournalBiology
Volume11
Issue number3
DOIs
StatePublished - Mar 2022

Bibliographical note

Funding Information:
Funding: This work was supported by National Institutes of Health Grant NIDDK (R21DK112144, R01DK115720), Regenerative Medicine Minnesota, and IBP start-up funds to EUA and T32 training grant (T32DK108733) to M.M.

Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

  • Acute pancreatitis
  • Cerulein
  • Inflammation
  • O-GlcNAc transferase (OGT)
  • O-GlcNAcylation
  • Pancreas
  • Pancreatitis

PubMed: MeSH publication types

  • Journal Article

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