Notch Signaling Is Required for Exocrine Regeneration After Acute Pancreatitis
Open accessAbstract
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 rol…
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Augmented Hedgehog, Notch, and Wnt/b-catenin signaling are mandatory for regeneration in mice after experimental induction of pancreatitis.
“Among others, augmented Hedgehog, Notch, and Wnt/b-catenin signaling were delineated as mandatory for regeneration in mice after experimental induction of pancreatitis [21–24].”
From TBX3 is dynamically expressed in pancreatic organogenesis and fine-tunes regeneration (2023) · cites this paper as [23]
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TBX3 is dynamically expressed in pancreatic organogenesis and fine-tunes regeneration
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- Authors
- Siveke, J. T., Lubeseder–Martellato, C., Lee, M., Mazur, P. K., Nakhai, H., Radtke, F., & Schmid, R. M.
- Affiliations
- TUM Klinikum (DE)
- École Polytechnique Fédérale de Lausanne (CH)
- Corresponding author
- Schmid, Roland M.
- ORCID
- Venue
- Gastroenterology
- Publisher
- Elsevier BV
- Published
- 2008-02
- Volume
- 134
- Issue
- 2
- Pages
- 544-555.e3
- ISSN
- 0016-5085 (ISSN-L)
- OpenAlex
- W2124018740
- Cited by
- 162
- References
- 3
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 3 · 2023: 8 · 2022: 6 · 2021: 9 · 2020: 6 · 2019: 3 · 2018: 10 · 2017: 6 · 2016: 14 · 2015: 7 · 2014: 12 · 2013: 10 · 2012: 13
- FWCI
- 16.86
- Type
- journal article
- Language
- en
- Open access
- green
- infoscience.epfl.ch
- Locations
- Gastroenterology (publishedVersion)
- PubMed (publishedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
- mediaTUM – the media and publications repository of the Technical University Munich (Technical University Munich) (submittedVersion)
- Topics
- Health Sciences › Medicine › Surgery › Pancreatitis Pathology and Treatment
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
- Keywords
- Notch signaling, acute pancreatitis, Notch1, β-catenin, Wnt signaling, cerulein-induced pancreatitis, gamma-secretase inhibition, conditional knockout mice
- MeSH terms
- Acute Disease, Animals, Ceruletide, Dibenzazepines, Disease Models, Animal, Mice, Inbred C57BL, Pancreatic Neoplasms, Pancreatitis, Regeneration, Signal Transduction, Mice, Knockout, Cell Line, Tumor, Pancreas, Exocrine, Wnt Proteins, beta Catenin, Mice, Receptor, Notch1, Amyloid Precursor Protein Secretases
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