23690540 OR Aryl hydrocarbon receptor negatively regulates expression of the plakoglobin gene (jup) Dotaz Zobrazit nápovědu
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.
- MeSH
- buněčná adheze MeSH
- buněčné linie MeSH
- DNA primery MeSH
- down regulace MeSH
- gama-katenin genetika MeSH
- klonování DNA MeSH
- krysa rodu rattus MeSH
- kvantitativní polymerázová řetězová reakce MeSH
- polychlorované dibenzodioxiny farmakologie MeSH
- potkani inbrední F344 MeSH
- proliferace buněk MeSH
- promotorové oblasti (genetika) MeSH
- receptory aromatických uhlovodíků fyziologie MeSH
- regulace genové exprese fyziologie MeSH
- sekvence nukleotidů MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH