Inducible expression of Wnt genes during adult hepatic stem/progenitor cell response
Open accessAbstract
In injured livers where hepatocyte growth is severely limited, facultative hepatic stem/progenitor cells, termed oval cells in rodents, are known to emerge and contribute to the regeneration process. Here, we investigated a possible involvement of Wnt signaling during mouse oval cell response and found significant upregulation of several Wnt genes including Wnt7a, Wnt7b, and Wnt10a. Accordingly, increase of beta-catenin protein was observed in oval cell compartments. Pharmacological activation of the canonical Wnt/beta-catenin signaling induced proliferation of cultured hepatic stem/progenitor cell lines. These results together implicate the role of Wnt/beta-catenin signaling in adult hepatic stem/progenitor cell response.
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In response to cholestatic injury, BECs upregulate WNT ligands.
“In response to cholestatic injury, BECs upregulate WNT ligands.57,94,109,110”
From Distinct hepatocyte identities in liver homeostasis and regeneration (2023) · cites this paper as [109]
The Results and discussion report strong upregulation of Wnt7a, Wnt7b, and Wnt10a in the livers of DDC-fed mice during an injury-induced oval-cell response. They do not establish that biliary epithelial cells (BECs) themselves upregulate those ligands; the Introduction describes DDC-induced injury as severe chronic liver injury, not specifically as cholestatic injury. (LLM, conf=0.86)
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Slusarski, D. C., Corces, V. G., & Moon, R. T. (1997) · Nature · doi:10.1038/37138 · Cited by 680 · see citing works
Wnt signaling through Dishevelled, Rac and JNK regulates dendritic development
Rosso, S. B., Sussman, D., Wynshaw-Boris, A., & Salinas, P. C. (2005) · Nature Neuroscience · doi:10.1038/nn1374 · Cited by 485 · cited 1× · see citing works
“Notably, it has been reported that Wnt7a and Wnt7b can activate the JNK pathway in endometrial cancer cells and hippocampal neurons, respectively [22,23], while Fzd2 has been shown to mediate activation of non-canonical signaling pathways in certain types of cells [21,24– 26].”
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Potential hepatic stem cells reside in EpCAM+ cells of normal and injured mouse liver
Okabe, M., Tsukahara, Y., Tanaka, M., Suzuki, K., Saito, S., Kamiya, Y., Tsujimura, T., Nakamura, K., & Miyajima, A. (2009) · Development · doi:10.1242/dev.031369 · Cited by 287 · see citing works
Self-citationDistinct hepatocyte identities in liver homeostasis and regeneration
Chen, F., Schönberger, K., & Tchorz, J. S. (2023) · JHEP Reports · doi:10.1016/j.jhepr.2023.100779 · Cited by 30 · see citing works
- Authors
- Itoh, T., Kamiya, Y., Okabe, M., Tanaka, M., & Miyajima, A.
- Affiliations
- The University of Tokyo (JP)
- Corresponding author
- Itoh, Tohru
- Venue
- FEBS Letters
- Publisher
- Wiley
- Published
- 2009-01-26
- Volume
- 583
- Issue
- 4
- Pages
- 777-781
- ISSN
- 0014-5793 (ISSN-L)
- 1873-3468
- OpenAlex
- W2133385241
- Cited by
- 50
- References
- 2
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 1 · 2023: 3 · 2022: 1 · 2021: 2 · 2020: 3 · 2019: 1 · 2018: 5 · 2017: 3 · 2016: 2 · 2015: 5 · 2014: 6 · 2013: 3 · 2012: 3
- FWCI
- 2.59
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- FEBS Letters (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ministry of Education, Culture, Sports, Science and Technology (CREST, 17014016)
- University of Tokyo
- Japan Society for the Promotion of Science (CREST, 17014016)
- Japan Science and Technology Agency (CREST)
- Institute of Molecular and Cell Biology
- Core Research for Evolutional Science and Technology
- Topics
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
- Health Sciences › Medicine › Rehabilitation › Wound Healing and Treatments
- Keywords
- Wnt signaling, β-catenin, hepatic progenitor cells, oval cells, liver regeneration, hepatocyte proliferation, Wnt7a, Wnt7b, WNT10A, liver injury
- MeSH terms
- Epithelial Cell Adhesion Molecule, Animals, Antigens, Neoplasm, Benzimidazoles, Cells, Cultured, Dicarbethoxydihydrocollidine, Fluorescent Dyes, Gene Expression Regulation, Immunohistochemistry, Liver, Luciferases, Male, Mice, Inbred C57BL, Stem Cells, Transfection, Signal Transduction, Cell Adhesion Molecules, Genes, Reporter, DNA, Complementary, Cell Proliferation, Wnt Proteins, Mice
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