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Cited by 24Liver physiology and pathologyOrgan Transplantation Techniques and OutcomesTissue Engineering and Regenerative Medicine

Impaired liver regeneration after hepatectomy and bleeding is associated with a shift from hepatocyte proliferation to hypertrophy

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Matot, Idit, Nachmansson, Nathalie, Duev, Omri, Schulz, Susanne, Schroeder‐Stein, Katrin, Frede, Stilla, Abramovitch, Rinat·2017·The FASEB Journal
DOI 10.1096/fj.201700153rPMC PMC5690394
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Abstract

Extensive liver resections are common, and bleeding is frequent in these operations. Impaired regeneration after partial hepatectomy (PHx) may contribute to liver failure. We thus assessed the impact of acute bleeding on the liver regeneration progress after PHx and explored possible contributing molecular mechanisms. In rats, the regeneration progress was delayed and attenuated with PHx and bleeding and was not restored with colloid resuscitation. Livers restored their initial volume by postoperative day (POD) 2 after PHx through hepatocyte proliferation vs. POD 4 in the PHx and bleeding group, primarily by hepatocyte hypertrophy. With bleeding, hepatocyte proliferation was hindered in two mechanisms: by inhibiting cells from starting proliferation and by causing hindrance in G 1 /S progression. Liver hypoxia was prominent, with significant prolonged up‐regulation of hypoxia‐inducible factors (HIF) and HIF‐targeted genes only in the PHx and bleeding group. Gene expression profiling revealed alterations in numerous genes that belong to critical pathways, including cell cycle, DNA replication, PI3K‐Akt, purine, and pyrimidine metabolism. Because liver surgery is frequently performed in patients with a predamaged liver, an improper regenerative process after PHx and bleeding might lead to decompensation. The results hint at specific pathways to target in order to improve liver regeneration during PHx and bleeding.—Matot, I., Nachmansson, N., Duev, O., Schulz, S., Schroeder‐Stein, K., Frede, S., Abramovitch, R. Impaired liver regeneration after hepatectomy and bleeding is associated with a shift from hepatocyte proliferation to hypertrophy. FASEB J. 31, 5283–5295 (2017). www.fasebj.org

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  • More recent evidence highlights hypertrophy as a critical compensatory mechanism, particularly in cases where proliferation is delayed or suppressed.

    “more recent evidence highlights hypertrophy as a critical, compensatory mechanism, particularly in cases where proliferation is delayed or suppressed[5,6].”

    From Liver regeneration after partial hepatectomy: Triggers and mechanisms (2025) · cites this paper as [6]

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Authors
Matot, I., Nachmansson, N., Duev, O., Schulz, S., Schroeder‐Stein, K., Frede, S., & Abramovitch, R.
Affiliations
  • Tel Aviv University (IL)
  • Hadassah Medical Center (IL)
  • University Hospital Bonn (DE)
Corresponding author
Abramovitch, Rinat
ORCID
Venue
The FASEB Journal
Publisher
Wiley
Published
2017-08-08
Volume
31
Issue
12
Pages
5283-5295
ISSN
  • 0892-6638 (ISSN-L)
  • 1530-6860
DOI
10.1096/fj.201700153r
PMC
PMC5690394
OpenAlex
W2742620842
Cited by
24
References
1
Citations by year
2025: 3 · 2024: 1 · 2023: 3 · 2022: 7 · 2021: 4 · 2020: 4 · 2019: 2
FWCI
1.01
Type
journal article
Language
en
Open access
Licence
Locations
  • The FASEB Journal (publishedVersion, cc-by-nc)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
Funders
  • Israel Science Foundation (1157/12)
  • Ministry of Health, State of Israel (3‐10999)
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
liver regeneration, partial hepatectomy, postoperative bleeding, hepatocyte proliferation, hepatocyte hypertrophy, liver hypoxia, hypoxia-inducible factor, G1/S cell cycle arrest, colloid resuscitation, gene expression profiling, PI3K/Akt signaling, purine and pyrimidine metabolism, liver failure
MeSH terms
Animals, DNA Replication, Hemorrhage, Hepatectomy, Hypertrophy, Liver Regeneration, Male, Rats, Wistar, DNA Methylation, Phosphatidylinositol 3-Kinases, Reverse Transcriptase Polymerase Chain Reaction, Oligonucleotide Array Sequence Analysis, Hepatocytes, Cell Proliferation, Rats, TOR Serine-Threonine Kinases, Transcriptome

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