Abstract | BACKGROUND & AIMS: METHODS: AP was induced in transgenic mice overexpressing BTC (BTC-tg), control mice, or control mice after administration of recombinant BTC. The severity of pancreatitis was assessed by measurements of serum amylase and lipase and histologic grading. The involvement of the stress-activated protein kinase (SAPK) was evaluated by treating BTC-tg mice with an SAPK inhibitor before induction of AP. RESULTS: BTC-tg mice showed increased apoptosis and proliferation in the exocrine pancreas, indicating an increased cell turnover. There was a marked, epidermal growth factor receptor-independent decrease in pancreas weight. After induction of AP by cerulein injection, BTC-tg mice showed a significantly lower increase in serum amylase and lipase levels as well as less pronounced tissue necrosis, edema, and inflammation, as compared to nontransgenic littermates. This protective effect, also confirmed in the L-arginine AP model, was associated with increased phosphorylation of SAPK and abrogated after treatment of BTC-tg mice with a SAPK inhibitor. Finally, the protective effect of BTC against AP was confirmed by treating nontransgenic mice with recombinant BTC. CONCLUSIONS: These findings indicate a potential application of the BTC/ERBB4 pathway for modulating the course of AP.
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Authors | Maik Dahlhoff, Hana Algül, Jens T Siveke, Marina Lesina, Rüdiger Wanke, Thomas Wartmann, Walter Halangk, Roland M Schmid, Eckhard Wolf, Marlon R Schneider |
Journal | Gastroenterology
(Gastroenterology)
Vol. 138
Issue 4
Pg. 1585-94, 1594.e1-3
(Apr 2010)
ISSN: 1528-0012 [Electronic] United States |
PMID | 20038432
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | 2010 AGA Institute. Published by Elsevier Inc. All rights reserved. |
Chemical References |
- Anthracenes
- Betacellulin
- Btc protein, mouse
- Intercellular Signaling Peptides and Proteins
- pyrazolanthrone
- ErbB Receptors
- Erbb4 protein, mouse
- Receptor, ErbB-4
- JNK Mitogen-Activated Protein Kinases
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Topics |
- Acute Disease
- Animals
- Anthracenes
(pharmacology)
- Apoptosis
- Betacellulin
- Cell Proliferation
- ErbB Receptors
(physiology)
- Intercellular Signaling Peptides and Proteins
(physiology)
- JNK Mitogen-Activated Protein Kinases
(physiology)
- Mice
- Mice, Transgenic
- Pancreas
(pathology)
- Pancreatitis
(pathology, prevention & control)
- Receptor, ErbB-4
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