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Temporal Analysis of Hepatocyte Differentiation by Small Hepatocyte-Like Progenitor Cells during Liver Regeneration in Retrorsine-Exposed Rats
- Source :
- The American Journal of Pathology. 157:771-786
- Publication Year :
- 2000
- Publisher :
- Elsevier BV, 2000.
-
Abstract
- Liver regeneration after two-thirds surgical partial hepatectomy (PH) in rats treated with the pyrrolizidine alkaloid retrorsine is accomplished through the activation, expansion, and differentiation of a population of small hepatocyte-like progenitor cells (SHPCs). We have examined expression of the major liver-enriched transcription factors, cytochrome P450 (CYP) enzymes, and other markers of hepatocytic differentiation in SHPCs during the protracted period of liver regeneration after PH in retrorsine-exposed rats. Early-appearing SHPCs (at 3-7 days after PH) express mRNAs for all of the major liver-enriched transcription factors at varying levels compared to fully differentiated hepatocytes. In addition, SHPCs lack (or have significantly reduced) expression of mRNA for hepatocyte markers tyrosine aminotransferase and alpha-1 antitrypsin, but their expression levels of mRNA and/or protein for WT1 and alpha-fetoprotein (AFP) are increased. With the exception of AFP expression, SHPCs resembled fully differentiated hepatocytes by 14 days after PH. Expression of AFP was maintained by most SHPCs through 14 days after PH, gradually declined through 23 days after PH, and was essentially absent from SHPC progeny by 30 days after PH. Furthermore, early appearing SHPCs lack (or have reduced expression) of hepatic CYP proteins known to be induced in rat livers after retrorsine exposure. The resistance of SHPCs to the mitoinhibitory effects of retrorsine may be directly related to a lack of CYP enzymes required to metabolize retrorsine to its toxic derivatives. These results suggest that SHPCs represent a unique parenchymal (less differentiated) progenitor cell population of adult rodent liver that is phenotypically distinct from fully differentiated hepatocytes, biliary epithelial cells, and (ductular) oval cells.
- Subjects :
- Male
Time Factors
Dipeptidyl Peptidase 4
Cellular differentiation
Population
Biology
Pathology and Forensic Medicine
Immunoenzyme Techniques
Tyrosine aminotransferase
Cytochrome P-450 Enzyme System
medicine
Animals
Hepatectomy
RNA, Messenger
Progenitor cell
WT1 Proteins
education
Pyrrolizidine Alkaloids
DNA Primers
Tyrosine Transaminase
Hepatocyte differentiation
education.field_of_study
Reverse Transcriptase Polymerase Chain Reaction
Stem Cells
Cell Differentiation
Antineoplastic Agents, Phytogenic
Molecular biology
Rats, Inbred F344
Liver regeneration
Liver Regeneration
Rats
DNA-Binding Proteins
medicine.anatomical_structure
Liver
Biochemistry
alpha 1-Antitrypsin
Hepatocyte
RNA
alpha-Fetoproteins
Stem cell
Biomarkers
Transcription Factors
Regular Articles
Subjects
Details
- ISSN :
- 00029440
- Volume :
- 157
- Database :
- OpenAIRE
- Journal :
- The American Journal of Pathology
- Accession number :
- edsair.doi.dedup.....cbdffe57f583ac1548d2e722db390cbd