Ah Receptor-Regulated Gene Expression During Experimental Liver Fibrosis
Abstract
The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor involved in numerous physiological processes, such as apoptosis, cell cycle regulation, and development. We recently established that activation of the AhR by the potent exogenous agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exacerbates liver damage and fibrogenesis in two murine models of experimental liver fibrosis. We hypothesize that AhR-mediated changes in gene expression underlie the exacerbation of fibrosis in TCDD-treated mice. The goal of this project was to use a commercially available PCR array to profile the expression of 84 key genes involved in the three phases of wound healing: inflammation, granulation, and tissue remodeling. Data were analyzed to compare gene expression in the liver of TCDD-treated and control mice in each fibrosis model. Results indicate that TCDD treatment increased expression of genes involved in all three phases of fibrosis. Furthermore, genes that were modulated by TCDD were found to contain AhR response elements, which further supports the notion that these genes are direct targets of AhR transcriptional activity during liver fibrosis.