Gene expression changes in rat liver following exposure to liver growth agents: role of Kupffer cells in xenobiotic-mediated liver growth
| Autor: | Nick Plant, Kathryn E. Plant, Peter G. Lord, Jon Lyon, G. Gordon Gibson, Kerstin Kramer, Sarah E Crunkhorn |
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| Rok vydání: | 2004 |
| Předmět: |
Male
medicine.medical_specialty Kupffer Cells medicine.medical_treatment Gene Expression Peroxisome Proliferation Apoptosis Biology Polymerase Chain Reaction Biochemistry Dexamethasone Xenobiotics Rats Sprague-Dawley chemistry.chemical_compound Internal medicine Gene expression medicine Animals Humans Cyproterone Acetate Pharmacology Hyperplasia Cell growth Kupffer cell Cyproterone acetate Organ Size medicine.disease Rats Pyrimidines Endocrinology medicine.anatomical_structure Cytokine Liver chemistry Cell Division |
| Zdroj: | Biochemical Pharmacology. 67:107-118 |
| ISSN: | 0006-2952 |
| DOI: | 10.1016/j.bcp.2003.09.001 |
| Popis: | Many xenobiotics are known to cause liver enlargement and hepatocarcinogenesis in rats, although the molecular mechanisms that underlie this effect remain largely undefined. Human exposure to several of these compounds, including glucocorticoids and peroxisome proliferators may be significant, due to their use in both pharmaceutical and industrial processes. It is therefore important to elucidate the molecular mechanisms underlying this abnormal liver enlargement in rats, as this will enable more accurate extrapolation of the possible outcomes of human exposure. Male Sprague–Dawley rats were dosed with the peroxisome proliferator Wy-14,643 and changes in liver gene expression examined using subtractive suppression hybridisation examined either 12 of 24 hr later. Twenty-five transcripts were identified which showed differential gene expression in liver following exposure toWy-14,643. Biochemical indices of liver growth (DNA synthesis, apoptosis) showed that these changes correlated with the initiation of liver enlargement. Rats were next treated with either Wy-14,643, cyproterone acetate and dexamethasone, chemically and mechanistically-distinct hepatomegalic compounds. Carboxylesterase and Kupffer cell receptor mRNA levels were seen to alter in a qualitatively similar fashion for all three compounds, and in a liver specific fashion. In addition, these changes correlated with a decrease in the density of Kupffer cells within the liver, which are known to release mitogenic cytokines, and have been linked to Wy-14,643-induced cell proliferation. We therefore propose that Kupffer cells play a role in a general mechanism of xenobiotic-mediated liver enlargement. |
| Databáze: | OpenAIRE |
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