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  4. Notch signaling is required for exocrine regeneration after acute pancreatitis
 
research article

Notch signaling is required for exocrine regeneration after acute pancreatitis

Siveke, J.T.
•
Lubeseder-Martellato, C.
•
Lee, M.
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2008
Gastroenterology

BACKGROUND & AIMS: The mechanisms for tissue regeneration and renewal after acute pancreatitis are not well understood but may involve activation of Notch signaling. To study the effect of Notch signaling ablation during acute experimental pancreatitis, we used a chemical and genetic approach to ablate Notch signaling in cerulein-induced pancreatitis in mice. METHODS: Acute pancreatitis was induced by cerulein treatment in mice treated with the gamma-secretase inhibitor dibenzazepine or in conditional Notch1 knockout mice. Mice were characterized using immunohistologic, biochemical, and molecular methods. To investigate Notch and beta-catenin interaction, acinar 266-6 cells were analyzed using transfection and biochemical assays. RESULTS: Loss of Notch signaling results in impaired regeneration after acute pancreatitis with fewer mature acinar cells in dibenzazepine-treated and Notch1-deficient mice in the regenerative phase 3 days after induction. beta-catenin expression was increased and prolonged during exocrine regeneration. Crosstalk between Notch and beta-catenin-mediated signaling was identified, with Notch1-IC inhibiting beta-catenin-mediated transcriptional activity. This inhibition was dependent on a functional RAM domain. CONCLUSIONS: Inhibition of Notch signaling in vivo leads to impaired regeneration of the exocrine pancreas after acute pancreatitis. Our results suggest an interaction of Notch and Wnt signaling in pancreatic acinar cells, providing evidence for a role of these pathways in the regulation of the maturation process of acinar cells.

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Type
research article
DOI
10.1053/j.gastro.2007.11.003
Web of Science ID

WOS:000253032900024

Author(s)
Siveke, J.T.
•
Lubeseder-Martellato, C.
•
Lee, M.
•
Mazur, P.K.
•
Nakhai, H.
•
Radtke, F.  
•
Schmid, R.M.
Date Issued

2008

Published in
Gastroenterology
Volume

134

Issue

2

Start page

544

End page

555

Editorial or Peer reviewed

REVIEWED

Written at

EPFL

EPFL units
UPRAD  
Available on Infoscience
October 2, 2008
Use this identifier to reference this record
https://infoscience.epfl.ch/handle/20.500.14299/30066
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