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Cited by 320Liver physiology and pathologyOrgan Transplantation Techniques and OutcomesTissue Engineering and Regenerative Medicine

The EGF receptor is required for efficient liver regeneration

Open access
Natarajan, Anuradha, Wagner, Bettina, Sibilia, Maria·2007·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.0704126104PMC PMC2040457
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Abstract

Mice lacking the EGF receptor (EGFR) die between midgestation and postnatal day 20 with various defects in neural and epithelial organs. Here, we generated mice carrying a floxed EGFR allele to inactivate the EGFR in fetal and adult liver. Perinatal deletion of EGFR in hepatocytes resulted in decreased body weight, whereas deletion in the adult liver did not affect body mass. Although liver function was not affected, after partial hepatectomy mice lacking EGFR in the liver showed increased mortality accompanied by increased levels of serum transaminases indicating liver damage. Liver regeneration was delayed in the mutants because of reduced hepatocyte proliferation. Analysis of cell cycle progression in EGFR-deficient livers indicated a defective G 1 –S phase entry with delayed transcriptional activation and reduced protein expression of cyclin D1 followed by reduced cdk2 and cdk1 expression. Impaired liver regeneration was accompanied by compensatory up-regulation of TNFα in the serum and prolonged activation of c-Jun. Moreover, p38α and NF-κB activation was reduced in regenerating mutant livers, indicating an impaired stress response after hepatectomy. Our studies demonstrate that EGFR is a critical regulator of hepatocyte proliferation in the initial phases of liver regeneration.

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  • EGFR signaling on hepatocytes is essential to liver regeneration.

    “Although EGFR signaling on hepatocytes is essential to liver regeneration 64”

    From Amphiregulin from regulatory T cells promotes liver fibrosis and insulin resistance in non-alcoholic steatohepatitis (2024) · cites this paper as [64]

    The Abstract identifies hepatocyte EGFR as critical for efficient proliferation during the initial phases of regeneration. But the Results (“Liver Regeneration Is Impaired in the Absence of EGFR”) report that mutant livers completed regeneration after an initial delay, so “essential to liver regeneration” overstates the finding. (LLM, conf=0.90)

    Experimental — accuracy not yet measured

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Cited by

Sorted by citations

Authors
Natarajan, A., Wagner, B., & Sibilia, M.
Affiliations
Medical University of Vienna (AT)
ORCID
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
2007-10-23
Volume
104
Issue
43
Pages
17081-17086
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.0704126104
PMC
PMC2040457
OpenAlex
W1973261871
Cited by
320
References
5
Citations by year
2026: 11 · 2025: 15 · 2024: 12 · 2023: 11 · 2022: 11 · 2021: 16 · 2020: 18 · 2019: 19 · 2018: 19 · 2017: 15 · 2016: 17 · 2015: 23 · 2014: 20 · 2013: 19 · 2012: 25
FWCI
10.89
Type
journal article
Language
en
Update notices
correction (2007-12-04)
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Hepatology › Liver physiology and pathology
  • Health Sciences › Medicine › Surgery › Organ Transplantation Techniques and Outcomes
  • Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
Keywords
EGF receptor, liver regeneration, hepatocyte proliferation, partial hepatectomy, cyclin D1, CDK2, CDK1, cell cycle progression, TNF-α, c-Jun, p38 MAPK, NF-κB, stress response, floxed allele, conditional knockout mice
MeSH terms
Alleles, Animals, Cell Cycle, Hepatectomy, Liver, Liver Regeneration, Signal Transduction, Cytokines, Gene Deletion, Gene Targeting, Hepatocytes, Cell Proliferation, Mice, ErbB Receptors

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