Aryl Hydrocarbon Receptor Negatively Regulates Expression of the Plakoglobin Gene (Jup)
Autor: | Jiří Kohoutek, Jiří Pacherník, Miroslav Machala, Dominika Sýkorová, Jiřina Procházková, Markéta Kabátková, Alois Kozubík, Eva Hrubá, Pavlína Šimečková, Lenka Šmerdová, Jan Vondráček |
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Rok vydání: | 2013 |
Předmět: |
Small interfering RNA
Polychlorinated Dibenzodioxins Down-Regulation Plakoglobin Biology Real-Time Polymerase Chain Reaction Toxicology Cell Line Adherens junction 03 medical and health sciences 0302 clinical medicine Gene expression Cell Adhesion Animals Cloning Molecular Progenitor cell Promoter Regions Genetic Cell Proliferation DNA Primers 030304 developmental biology 0303 health sciences Gene knockdown Base Sequence Aryl hydrocarbon receptor Molecular biology Rats Inbred F344 Rats Gene Expression Regulation Receptors Aryl Hydrocarbon 030220 oncology & carcinogenesis biology.protein gamma Catenin Signal transduction |
Zdroj: | Toxicological Sciences. 134:258-270 |
ISSN: | 1096-0929 1096-6080 |
Popis: | Plakoglobin is an important component of intercellular junctions, including both desmosomes and adherens junctions, which is known as a tumor suppressor. Although mutations in the plakoglobin gene (Jup) and/or changes in its protein levels have been observed in various disease states, including cancer progression or cardiovascular defects, the information about endogenous or exogenous stimuli orchestrating Jup expression is limited. Here we show that the aryl hydrocarbon receptor (AhR) may regulate Jup expression in a cell-specific manner. We observed a significant suppressive effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a model toxic exogenous activator of the AhR signaling, on Jup expression in a variety of experimental models derived from rodent tissues, including contact-inhibited rat liver progenitor cells (where TCDD induces cell proliferation), rat and mouse hepatoma cell models (where TCDD inhibits cell cycle progression), cardiac cells derived from the mouse embryonic stem cells, or cardiomyocytes isolated from neonatal rat hearts. The small interfering RNA (siRNA)-mediated knockdown of AhR confirmed its role in both basal and TCDD-deregulated Jup expression. The analysis of genomic DNA located ~2.5kb upstream of rat Jup gene revealed a presence of evolutionarily conserved AhR binding motifs, which were confirmed upon their cloning into luciferase reporter construct. The siRNA-mediated knockdown of Jup expression affected both proliferation and attachment of liver progenitor cells. The present data indicate that the AhR may contribute to negative regulation of Jup gene expression in rodent cellular models, which may affect cell adherence and proliferation. |
Databáze: | OpenAIRE |
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