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Cited by 292Wnt/β-catenin signaling in development and cancerLiver physiology and pathologyPlanarian Biology and Electrostimulation

Changes in Wnt/β–Catenin Pathway During Regulated Growth in Rat Liver Regeneration

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Monga, Satdarshan P.S., Pediaditakis, Peter, Mule, Karen, Stolz, Donna Beer, Michalopoulos, George K.·2001·Hepatology
DOI 10.1053/jhep.2001.23786PMC PMC1821078
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Abstract

The wnt/beta-catenin pathway is important during embryogenesis and carcinogenesis. beta-Catenin interaction with E-cadherin has been shown to be crucial in cell-cell adhesion. We report novel findings in the wnt pathway during rat liver regeneration after 70% partial hepatectomy using Western blot analyses, immunoprecipitation studies, and immunofluorescence. We found wnt-1 and beta-catenin proteins to be predominantly localized in hepatocytes. Immediately following partial hepatectomy, we observed an initial increase in beta-catenin protein during the first 5 minutes with its translocation to the nucleus. We show this increase to be the result of decreased degradation of beta-catenin (decrease in serine phosphorylated beta-catenin) as seen by immunoprecipitation studies. We observed activation of beta-catenin degradation complex comprising of adenomatous polyposis coli gene product (APC) and serine-phosphorylated axin protein, beginning at 5 minutes after hepatectomy, leading to its decreased levels after this time. Quantitative changes observed in E-cadherin protein during liver regeneration are, in general, reverse to those seen in beta-catenin. In addition, using immunoprecipitation, we observe elevated levels of tyrosine-phosphorylated beta-catenin at 6 hours onward. Thus, changes in the wnt pathway during regulated growth seem to tightly regulate cytosolic beta-catenin levels and may be contributing to induce cell proliferation and target gene expression. Furthermore, these changes might also be intended to negatively regulate cell-cell adhesion for structural reorganization during the process of liver regeneration.

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  • Hepatocytes in the postnatal liver expand rapidly in a Wnt/β-catenin signaling-dependent way.

    “Hepatocytes in the postnatal liver expand rapidly in a Wnt/β-catenin signaling-dependent way (12–16).”

    From Wnt signaling regulates hepatocyte cell division by a transcriptional repressor cascade (2022) · cites this paper as [12]

    The Abstract describes rapid hepatocyte proliferation after partial hepatectomy in adult rats, and the Discussion links early β-catenin nuclear translocation to that regeneration. It does not study normal postnatal liver expansion, and it suggests Wnt/β-catenin signaling may contribute to proliferation rather than establishing that expansion depends on it. The indexed passages provide no page numbers. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • The postnatal liver expands rapidly in a Wnt/βcatenin signaling-dependent way and switches from initially containing diploid hepatocytes to becoming mostly polyploid.

    “The postnatal liver expands rapidly in a Wnt/βcatenin signaling-dependent way and switches from initially containing diploid hepatocytes to becoming mostly polyploid (Apte et al. 2007;Monga et al. 2001).”

    From Hepatocyte Cell Cycle Progression Depends on a Transcriptional Repressor Cascade Downstream of Wnt Signaling (2021) · cites this paper as Monga et al. 2001

    The Discussion describes changes in Wnt/β-catenin signaling during liver regrowth after partial hepatectomy in adult rats and suggests that β-catenin may help initiate cell proliferation. It does not establish that postnatal liver expansion depends on this pathway or describe a shift from diploid to mostly polyploid hepatocytes (searched: postnatal, diploid, polyploid). (LLM, conf=0.85)

    Experimental — accuracy not yet measured

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Authors
Monga, S. P. S., Pediaditakis, P., Mule, K., Stolz, D. B., & Michalopoulos, G. K.
Affiliations
University of Pittsburgh (US)
Corresponding author
Michalopoulos, George K.
ORCID
Venue
Hepatology
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2001-05
Volume
33
Issue
5
Pages
1098-1109
ISSN
0270-9139 (ISSN-L)
DOI
10.1053/jhep.2001.23786
PMC
PMC1821078
OpenAlex
W2129981597
Cited by
292
References
66
Citations by year
2026: 6 · 2025: 15 · 2024: 12 · 2023: 11 · 2022: 7 · 2021: 15 · 2020: 16 · 2019: 7 · 2018: 12 · 2017: 10 · 2016: 9 · 2015: 10 · 2014: 14 · 2013: 13 · 2012: 10
FWCI
2.33
Type
journal article
Language
en
Open access
Licence
doi.wiley.com/10.1002/tdm_license_1.1 (tdm, 5236 d)
Locations
  • Hepatology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health (CA30241)
  • National Cancer Institute (CA 35373, R01CA035373, CA30241)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
  • Health Sciences › Medicine › Hepatology › Liver physiology and pathology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Planarian Biology and Electrostimulation
Keywords
Wnt/β-catenin signaling, liver regeneration, partial hepatectomy, β-catenin degradation, serine phosphorylation, tyrosine phosphorylation, E-cadherin, Axin, adenomatous polyposis coli, hepatocytes, cell-cell adhesion, cell proliferation
MeSH terms
Animals, Biological Transport, Cytoskeletal Proteins, Liver, Liver Regeneration, Male, Phosphorylation, Proteins, Proto-Oncogene Proteins, Rats, Inbred F344, Reference Values, Repressor Proteins, Time Factors, Tissue Distribution, Tyrosine, Trans-Activators, Cadherins, Zebrafish Proteins, Wnt Proteins, Wnt1 Protein, beta Catenin, Rats, Axin Protein

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