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ATP binding cassette transporter gene expression in rat liver progenitor cells
J E Ros1, T A D Roskams, M Geuken
1Groningen University Institute for Drug Exploration (GUIDE), Centre for the Study of Liver, Digestive, and Metabolic Diseases, University Hospital Groningen, 9700 RB Groningen, the Netherlands.
Gut
|June 13, 2003
Summary
Hepatic progenitor cells (HPCs) express high levels of multidrug resistance-associated protein 1 (MRP1) and MRP3. These ATP binding cassette (ABC) transporters may protect HPCs during severe liver damage.
Area of Science:
- Hepatology
- Cell Biology
- Molecular Biology
Background:
- Liver regeneration relies on hepatic progenitor cells (HPCs) that must survive toxic liver conditions.
- ATP binding cassette (ABC) transporters are efflux pumps that may protect cells.
Purpose of the Study:
- To determine the ABC transporter phenotype of hepatic progenitor cells (HPCs).
Main Methods:
- HPC activation was induced in rats using 2-acetylaminofluorene (2-AAF) and partial hepatectomy (PHx).
- ABC transporter gene expression was analyzed using RT-PCR in isolated cells and immunohistochemistry in liver samples.
- Efflux activity of ABC transporters was assessed in cultured progenitor cells via flow cytometry.
Main Results:
- Rats treated with 2-AAF/PHx showed increased mRNA levels for Mdr1b, Mrp1, and Mrp3.
- Immunohistochemistry revealed Mrp1 and Mrp3 expression in progenitor cells and Mdr1b in hepatocytes.
- Isolated HPCs and cultured progenitor cells predominantly expressed Mrp1 and Mrp3 mRNA, with minimal expression of hepatocyte-specific transporters.
Conclusions:
- Hepatic progenitor cells (HPCs) exhibit high expression of active Mrp1 and Mrp3.
- These transporters likely play a cytoprotective role for HPCs in hepatotoxic environments.
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