Reduction in O-GlcNAcylation Mitigates the Severity of Inflammatory Response in Cerulein-Induced Acute Pancreatitis in a Mouse Model
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 tran...
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MDPI AG
2022-02-01
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| Series: | Biology |
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| Online Access: | https://www.mdpi.com/2079-7737/11/3/347 |
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| author | Mackenzie Moore Nandini Avula Alicia Wong Megan Beetch Seokwon Jo Emilyn U. Alejandro |
| author_facet | Mackenzie Moore Nandini Avula Alicia Wong Megan Beetch Seokwon Jo Emilyn U. Alejandro |
| author_sort | Mackenzie Moore |
| collection | DOAJ |
| description | 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<sup>Panc+/−</sup>) 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<sup>Panc+/−</sup> mice had decreased severity of AP. Additionally, serum lipase, LDH, and TNF-α in OGT<sup>Panc+/−</sup> 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. |
| first_indexed | 2024-03-09T20:06:31Z |
| format | Article |
| id | doaj.art-2788f7740e45478f86717dfd0d817d49 |
| institution | Directory Open Access Journal |
| issn | 2079-7737 |
| language | English |
| last_indexed | 2024-03-09T20:06:31Z |
| publishDate | 2022-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biology |
| spelling | doaj.art-2788f7740e45478f86717dfd0d817d492023-11-24T00:30:37ZengMDPI AGBiology2079-77372022-02-0111334710.3390/biology11030347Reduction in O-GlcNAcylation Mitigates the Severity of Inflammatory Response in Cerulein-Induced Acute Pancreatitis in a Mouse ModelMackenzie Moore0Nandini Avula1Alicia Wong2Megan Beetch3Seokwon Jo4Emilyn U. Alejandro5Department of Integrative Biology and Physiology, University of Minnesota Medical School, Minneapolis, MN 55455, USADepartment of Integrative Biology and Physiology, University of Minnesota Medical School, Minneapolis, MN 55455, USADepartment of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, MN 55455, USADepartment of Integrative Biology and Physiology, University of Minnesota Medical School, Minneapolis, MN 55455, USADepartment of Integrative Biology and Physiology, University of Minnesota Medical School, Minneapolis, MN 55455, USADepartment of Integrative Biology and Physiology, University of Minnesota Medical School, Minneapolis, MN 55455, USAAcute 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<sup>Panc+/−</sup>) 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<sup>Panc+/−</sup> mice had decreased severity of AP. Additionally, serum lipase, LDH, and TNF-α in OGT<sup>Panc+/−</sup> 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.https://www.mdpi.com/2079-7737/11/3/347O-GlcNAc transferase (OGT)O-GlcNAcylationpancreaspancreatitisacute pancreatitiscerulein |
| spellingShingle | Mackenzie Moore Nandini Avula Alicia Wong Megan Beetch Seokwon Jo Emilyn U. Alejandro Reduction in O-GlcNAcylation Mitigates the Severity of Inflammatory Response in Cerulein-Induced Acute Pancreatitis in a Mouse Model Biology O-GlcNAc transferase (OGT) O-GlcNAcylation pancreas pancreatitis acute pancreatitis cerulein |
| title | Reduction in O-GlcNAcylation Mitigates the Severity of Inflammatory Response in Cerulein-Induced Acute Pancreatitis in a Mouse Model |
| title_full | Reduction in O-GlcNAcylation Mitigates the Severity of Inflammatory Response in Cerulein-Induced Acute Pancreatitis in a Mouse Model |
| title_fullStr | Reduction in O-GlcNAcylation Mitigates the Severity of Inflammatory Response in Cerulein-Induced Acute Pancreatitis in a Mouse Model |
| title_full_unstemmed | Reduction in O-GlcNAcylation Mitigates the Severity of Inflammatory Response in Cerulein-Induced Acute Pancreatitis in a Mouse Model |
| title_short | Reduction in O-GlcNAcylation Mitigates the Severity of Inflammatory Response in Cerulein-Induced Acute Pancreatitis in a Mouse Model |
| title_sort | reduction in o glcnacylation mitigates the severity of inflammatory response in cerulein induced acute pancreatitis in a mouse model |
| topic | O-GlcNAc transferase (OGT) O-GlcNAcylation pancreas pancreatitis acute pancreatitis cerulein |
| url | https://www.mdpi.com/2079-7737/11/3/347 |
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