Aryl hydrocarbon receptor negatively regulates expression of the plakoglobin gene (jup)
Language English Country United States Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
23690540
DOI
10.1093/toxsci/kft110
PII: kft110
Knihovny.cz E-resources
- Keywords
- aryl hydrocarbon receptor, cardiomyocytes., cell proliferation, desmosomes, dioxin, liver progenitor cells, plakoglobin,
- MeSH
- Cell Adhesion MeSH
- Cell Line MeSH
- DNA Primers MeSH
- Down-Regulation MeSH
- gamma Catenin genetics MeSH
- Cloning, Molecular MeSH
- Rats MeSH
- Real-Time Polymerase Chain Reaction MeSH
- Polychlorinated Dibenzodioxins pharmacology MeSH
- Rats, Inbred F344 MeSH
- Cell Proliferation MeSH
- Promoter Regions, Genetic MeSH
- Receptors, Aryl Hydrocarbon physiology MeSH
- Gene Expression Regulation physiology MeSH
- Base Sequence MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- DNA Primers MeSH
- gamma Catenin MeSH
- Polychlorinated Dibenzodioxins MeSH
- Receptors, Aryl Hydrocarbon MeSH
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.
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