Hedgehog Signaling Is Required for Effective Regeneration of Exocrine Pancreas
Open accessAbstract
Although both endocrine and the exocrine pancreas display a significant capacity for tissue regeneration and renewal, the existence of progenitor cells in the adult pancreas remains uncertain. Using a model of cerulein-mediated injury and repair, we demonstrate that mature exocrine cells, defined by expression of an Elastase1 promoter, actively contribute to regenerating pancreatic epithelium through formation of metaplastic ductal intermediates. Acinar cell regeneration is associated with activation of Hedgehog (Hh) signaling, as assessed by up-regulated expression of multiple pathway components, as well as activation of a Ptch-lacZ reporter allele. Using both pharmacologic and genetic techniques, we also show that the ability of mature exocrine cells to accomplish pancreatic regeneration is impaired by blockade of Hh signaling. Specifically, attenuated regeneration in the absence of an intact Hh pathway is characterized by persistence of metaplastic epithelium expressing markers of pancreatic progenitor cells, suggesting an inhibition of redifferentiation into mature exocrine cells. Given the known role of Hh signaling in exocrine pancreatic cancer, these findings may provide a mechanistic link between injury-induced activation of pancreatic progenitors and subsequent pancreatic neoplasia.
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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 [22]
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- Authors
- Fendrich, V., Esni, F., Garay, M. V. R., Feldmann, G., Habbe, N., Jensen, J. N., Dor, Y., Stoffers, D., Jensen, J., Leach, S. D., & Maitra, A.
- Affiliations
- Johns Hopkins University (US)
- University of Pittsburgh (US)
- Hebrew University of Jerusalem (IL)
- University of Pennsylvania (US)
- Corresponding author
- Leach, Steven D.
- Maitra, Anirban
- Venue
- Gastroenterology
- Publisher
- Elsevier BV
- Published
- 2008-08
- Volume
- 135
- Issue
- 2
- Pages
- 621-631.e8
- ISSN
- 0016-5085 (ISSN-L)
- PMC
- PMC2666349
- OpenAlex
- W2165110092
- Cited by
- 191
- References
- 3
- Citations by year
- 2026: 5 · 2025: 3 · 2024: 7 · 2023: 8 · 2022: 6 · 2021: 13 · 2020: 9 · 2019: 6 · 2018: 13 · 2017: 11 · 2016: 9 · 2015: 8 · 2014: 18 · 2013: 13 · 2012: 22
- FWCI
- 5.07
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Gastroenterology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Deutscher Akademischer Austauschdienst
- National Institutes of Health (CA113669, DK072532)
- Vanderbilt University (U01CA084239)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Hedgehog Signaling Pathway Studies
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Keywords
- Hedgehog signaling, pancreatic progenitor cells, PTCH1, pancreatic neoplasia, tissue regeneration
- MeSH terms
- Smoothened Receptor, Animals, Ceruletide, Cell Differentiation, Cell Transformation, Neoplastic, Disease Models, Animal, Epithelial Cells, Intermediate Filament Proteins, Metaplasia, Mice, Inbred C57BL, Mice, Transgenic, Nerve Tissue Proteins, Pancreatic Ducts, Pancreatitis, Pancreatic Elastase, Regeneration, Stem Cells, Time Factors, Veratrum Alkaloids, Signal Transduction, Genes, Reporter, Receptors, G-Protein-Coupled, Pancreas, Exocrine, Cell Proliferation, Mice, Hedgehog Proteins, Nestin
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