Toxic compounds activating Ah receptor (AhR) present an important group of environmental polutants, which may have deleterious effects on both animal and human health. Analysis of signaling pathways affected by AhR enables to describe both the mechanisms being responsible for the toxic effects of these compounds and to contribute to understanding of the role of specific signaling modules in physiological and pathological processes. The proposed project will focuse on the analysis of interactions of AhR signaling and the processes controlled by Wnt signaling, which plays a crucial role in development, as well as e.g. in carcinogenesis. We will study interactions of both signaling pathways at the cellular level in regulation of expression of modell target genes, expression and activity of biotransformation enzymes and the factors modulating cell proliferation/cell death in modle liver and colon cells. The project will bring a novel information about the importance of AhR - Wnt interactions in toxic effects of AhR ligands, tumor development and in regulation of liver physiological functions. (en)
Základním cílem projektu je charakterizace interakcí signálních drah Ah receptoru a Wnt, která by mohla hrát roli v negativních účincích toxických environmentálních polutantů. Vzájemné interakce těchto dvou drah budou studovány především s využitím definovaných buněčných modelů in vitro.