Liver regeneration by small hepatocyte-like progenitor cells after necrotic injury by carbon tetrachloride in retrorsine-exposed rats
Abstract
Liver regeneration after partial hepatectomy (PH) in rats exposed to the pyrrolizidine alkaloid retrorsine is accomplished through the proliferation and differentiation of a population of small hepatocyte-like progenitor cells (SHPCs). The activation, emergence, and outgrowth of SHPCs in response to the liver deficit generated through surgical PH have been well characterized. However, the participation of these cells in the restoration of hepatocyte numbers and regeneration of liver tissue mass following necrotic injury has not been investigated. To investigate the capacity of SHPCs to respond to necrotizing liver injury, we combined retrorsine treatment with the centrilobular-specific toxin carbon tetrachloride (CCl(4)). Male Fischer 344 rats were treated with retrorsine (30 mg/kg ip) at 6 and 8 weeks of age, followed by CCl(4) treatment (1500 mg/kg ip) 5 weeks later. Liver tissues were harvested at 3, 7, 14, 21, and 30-days post-injection. The dose of CCl(4) employed resulted in the necrotic destruction of 59±2% of liver mass and elicited a regenerative response equivalent to that of surgical PH. Livers from retrorsine-exposed CCl(4)-treated rats exhibit SHPC proliferation similar to retrorsine-exposed rats subjected to PH (RP). SHPCs appear at 3-days post-injection, continue to expand at 7-days and 14-days post-injection, and completely regenerate/restore the liver mass and structure in these animals by 30-days post-injection. The magnitude of SHPC response observed in the…
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Small hepatocytes found in retrorsine-treated rat livers and small Thy1+ hepatocytes observed in rat livers following galactosamine-induced injury have robust regenerative properties.
“An interesting but less well understood population of hepatocytes are the small hepatocytes found in retrorsine-treated rat livers[138], [139], [140] and the small Thy1+ hepatocytes observed in rat livers following galactosamine-induced injury141 (Fig. 3F). These small hepatocytes were reported to have robust regenerative properties.”
From Distinct hepatocyte identities in liver homeostasis and regeneration (2023) · cites this paper as [139]
Cites
Michalopoulos, G. K. (2007) · Journal of Cellular Physiology · doi:10.1002/jcp.21172 · Cited by 1,384 · see citing works
Avril, A., Pichard, V., Bralet, M.-P., & Ferry, N. (2004) · Journal of Hepatology · doi:10.1016/j.jhep.2004.07.029 · Cited by 62 · see citing works
Best, D. H., & Coleman, W. B. (2007) · Journal of Hepatology · doi:10.1016/j.jhep.2007.01.040 · Cited by 35 · see citing works
Self-citationBest, H. D., & Coleman, W. B. (2007) · Hepatology · doi:10.1002/hep.21876 · Cited by 21 · see citing works
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Distinct 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
Sengupta, S., Johnson, B., Seirup, M., Ardalani, H., Duffin, B., Barrett-Wilt, G. A., Stewart, R., & Thomson, J. A. (2020) · Current Research in Toxicology · doi:10.1016/j.crtox.2020.08.001 · Cited by 9 · see citing works
- Authors
- Best, D. H., & Coleman, W. B.
- Affiliations
- University of North Carolina at Chapel Hill (US)
- Venue
- Experimental and Molecular Pathology
- Publisher
- Elsevier BV
- Published
- 2010-10
- Volume
- 89
- Issue
- 2
- Pages
- 92-98
- ISSN
- 0014-4800 (ISSN-L)
- OpenAlex
- W1980478182
- Cited by
- 13
- References
- 4
- Citations by year
- 2023: 1 · 2022: 1 · 2020: 2 · 2018: 1 · 2017: 1 · 2015: 2 · 2013: 1 · 2012: 1
- FWCI
- 1.04
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Experimental and Molecular Pathology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Cancer Institute (CA 78343)
- National Institute of Environmental Health Sciences (T32-ES07017, T32ES007017)
- Topics
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Keywords
- liver regeneration, carbon tetrachloride, retrorsine, liver necrosis, pyrrolizidine alkaloids, partial hepatectomy, progenitor cell proliferation, periportal zone, liver injury
- MeSH terms
- Animals, Carbon Tetrachloride, Hepatectomy, Liver Regeneration, Male, Necrosis, Pyrrolizidine Alkaloids, Random Allocation, Rats, Inbred F344, Stem Cells, Hepatocytes, Rats, Chemical and Drug Induced Liver Injury
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