1. Fetal skin fibroblasts: A cell model for studying the retinoid pathway in congenital diaphragmatic hernia
- Author
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Goumy, Carole, Coste, Karen, Marceau, Geoffroy, Gouas, Laetitia, Tchirkov, Andrei, Vago, Philippe, Gallot, Denis, Sapin, Vincent, Tchirkov, Andreï, Cytogénétique Médicale, CHU Clermont-Ferrand-Université d'Auvergne - Clermont-Ferrand I (UdA)-CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Faculté de Médecine - Clermont-Auvergne (FM - UCA), Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Génétique, Reproduction et Développement (GReD), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), Laoratoire de Biochimie, Physiopathologie et thérapie du muscle strié, Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR14-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER, Génétique Médicale, CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], Pôle Entrepreneuriat et Innovation - Rouen Business School, Rouen Business School, Laboratoire de Biochimie, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS)
- Subjects
Embryology ,medicine.medical_specialty ,medicine.drug_class ,Retinoic acid ,Gestational Age ,Tretinoin ,Context (language use) ,Biology ,03 medical and health sciences ,chemistry.chemical_compound ,Fetus ,Internal medicine ,medicine ,Humans ,RNA, Messenger ,Retinoid ,Receptor ,[SDV.BDD]Life Sciences [q-bio]/Development Biology ,Cells, Cultured ,Skin ,030304 developmental biology ,Hernia, Diaphragmatic ,0303 health sciences ,030302 biochemistry & molecular biology ,Gene Expression Regulation, Developmental ,Congenital diaphragmatic hernia ,General Medicine ,Fibroblasts ,medicine.disease ,3. Good health ,Retinoic acid receptor ,Retinoid X Receptors ,[SDV.BDD.EO]Life Sciences [q-bio]/Development Biology/Embryology and Organogenesis ,Endocrinology ,chemistry ,Nuclear receptor ,Pediatrics, Perinatology and Child Health ,Cancer research ,Signal transduction ,Hernias, Diaphragmatic, Congenital ,Signal Transduction ,Developmental Biology - Abstract
BACKGROUND Although there is strong evidence that genetic factors play a pathogenic role in congenital diaphragmatic hernia (CDH), few causal genes have been identified in humans. A number of studies, essentially in animal models, have suggested that disruption of the retinoid signaling pathway plays a major role in the pathogenesis of CDH. Our hypothesis is that human fetal skin fibroblasts express some metabolic and molecular actors of the retinoid pathway and that they offer convenient cellular material for investigating the molecular retinoid pathway defects associated with CDH. METHODS We first established the expression of receptors, enzymes and binding proteins involved in the retinoic acid (RA) pathway in non-CDH fetal skin fibroblasts using RT-PCR and immunocytochemistry approaches. We then studied the expression of these genes in skin fibroblasts from seven fetuses with isolated and nonisolated CDH. RESULTS Fetal skin fibroblasts expressed enzymes involved in RA metabolism as well as nuclear receptors for signal transduction. Basal levels of retinoic acid receptor, retinaldehyde dehydrogenase 2, and CYP26 (cytochrome P450 RAI) expression were altered in two of seven fetuses. Interestingly, these genes were previously described as abnormally expressed in CDH physiopathology. CONCLUSION Our results suggest that human fetal skin fibroblasts could be useful for studying retinoid signaling pathway disruption in the context of CDH. Our proposal is strengthened by the fact that we identified CDH fetuses for which molecular and metabolic actors of the retinoid pathway were not detected. Birth Defects Research (Part A), 2010. © 2010 Wiley-Liss, Inc.
- Published
- 2010