Co-cultures of enterocytes and hepatocytes for retinoid transport and metabolism
| Autor: | Maria Laura Scarino, Carlotta Rossi, Barbara Guantario, Diana Bellovino, Simonetta Ferruzza, Yula Sambuy, Christiane Guguen-Guillouzo |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
medicine.drug_class
Cellular differentiation Biology Toxicology Models Biological Cell Line CYP26A1 Mice Cytochrome P-450 Enzyme System medicine Animals Humans Secretion Retinoid RNA Messenger Secondary metabolism Vitamin A Biological Transport Cell Differentiation General Medicine Retinoic Acid 4-Hydroxylase beta Carotene In vitro Coculture Techniques Up-Regulation medicine.anatomical_structure Enterocytes Biochemistry Cell culture Hepatocyte Hepatocytes RNA Polymerase II |
| Zdroj: | Scopus-Elsevier |
| ISSN: | 1879-3177 |
| Popis: | Dietary retinoid bioavailability involves the interplay of the intestine (transport and metabolism) and the liver (secondary metabolism). To reproduce these processes in vitro, differentiated human intestinal Caco-2/TC7 cells were co-cultured with two hepatocyte cell lines. Murine 3A cells and the more highly differentiated human HepaRG hepatocytes were both shown to respond to β-carotene (BC) and retinol (ROH) treatment by secreting Retinol Binding Protein 4 (RBP4). In co-culture experiments, Caco-2/TC7 were differentiated on filter inserts and transferred for the time of the experiment to culture wells containing confluent 3A or differentiated HepaRG cells. Functionality of the co-cultures was assayed using as endpoints the retinol-dependent secretion of RBP4 and the retinoic acid-dependent induction of CYP26A1 in hepatocytes. BC and ROH added to intestinal Caco-2/TC7 induced a reduction in intracellular RBP4 levels in the underlying hepatocytes and its secretion into the medium. HepaRG hepatocytes were also shown to up-regulate the expression of CYP26A1 mRNA in response to retinoid treatment. This in vitro model represents a useful tool to analyze the absorption and metabolism of retinoids and could be further developed to investigate other dietary compounds and molecules of pharmacological interest. |
| Databáze: | OpenAIRE |
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