Treatment with 2-AAF blocks the small hepatocyte-like progenitor cell response in retrorsine-exposed rats
Open accessAbstract
Background/aims Liver regeneration after partial hepatectomy (PH) in retrorsine-exposed rats is accomplished through proliferation and differentiation of small hepatocyte-like progenitor cells (SHPCs). The cells of origin of SHPCs are not known. We investigated the possibility that SHPCs are directly derived from oval cells, a known liver progenitor cell, by combining the retrorsine/PH (RP) model with 2-acetamidofluorene (2-AAF), an anti-mitotic agent that elicits an oval cell reaction in response to liver deficit. Methods Male Fischer 344 rats were treated with retrorsine (30 mg/kg ip) at 6 and 8 weeks of age, with PH 5 weeks after the final treatment. Seven days prior to PH, a 21-day 2-AAF (50mg) time-release pellet was inserted subcutaneously. Livers were harvested at 3, 7, 10, 14, and 21-days post-PH. Results Liver sections from animals treated with 2-AAF/retrorsine/PH (2-AAF/RP) contain significant numbers of proliferating oval cells, but no SHPCs at 7-days post-PH, while RP animals exhibit significant numbers of SHPCs and minimal oval cell reaction. Between 10 and 14-days post-PH, new hepatocyte clusters appear in 2-AAF/RP treated rats. Labeling of proliferating oval cells with BrdU at 6-days post-PH demonstrated that these new hepatocytes represent the progeny of differentiating oval cells. Conclusions The observed differences in progenitor cell responses between 2-AAF/RP and RP animals strongly suggest that SHPCs are not the progeny of oval cell precursors, but represent an independent liver progenitor cell population.
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Hepatocytes are the source of small hepatocytes.
“a number of different approaches demonstrated that hepatocytes are the source of small hepatocytes.[143], [144], [145], [146]”
From Distinct hepatocyte identities in liver homeostasis and regeneration (2023) · cites this paper as [143]
The Introduction says the origin of small hepatocyte-like progenitor cells remains unknown and that studies suggest contradictory origins. The Discussion reports a study concluding that mature hepatocytes are their source, but says it failed to rule out contributions from other cell types. The paper therefore does not treat hepatocyte origin as demonstrated. (LLM, conf=0.88)
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- Authors
- Best, D. H., & Coleman, W. B.
- Affiliations
- University of North Carolina at Chapel Hill (US)
- Corresponding author
- Coleman, William B.
- Venue
- Journal of Hepatology
- Publisher
- Elsevier BV
- Published
- 2007-06
- Volume
- 46
- Issue
- 6
- Pages
- 1055-1063
- ISSN
- 0168-8278 (ISSN-L)
- PMC
- PMC1974854
- OpenAlex
- W1990242940
- Cited by
- 35
- References
- 34
- Citations by year
- 2023: 2 · 2021: 2 · 2017: 1 · 2016: 2 · 2014: 2 · 2013: 4
- FWCI
- 3.88
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Hepatology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
- UNC Libraries
- Funders
- National Institutes of Health (CA 78343)
- National Cancer Institute (CA 78343, R01CA078434, R01CA078343, R56CA078343)
- National Institute of Environmental Health Sciences (T32-ES07017, T32ES007017)
- Topics
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Health Sciences › Medicine › Surgery › Organ Transplantation Techniques and Outcomes
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
- Keywords
- liver regeneration, partial hepatectomy, retrorsine, 2-acetylaminofluorene, oval cells, liver progenitor cells, hepatocyte differentiation, antimitotic agents
- MeSH terms
- Animals, Antineoplastic Agents, Phytogenic, Carcinogens, Liver, Liver Regeneration, Male, Pyrrolizidine Alkaloids, Rats, Inbred F344, Regeneration, Stem Cells, 2-Acetylaminofluorene, Hepatocytes, Cell Proliferation, Antimitotic Agents, Rats
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