Consequences of TCDD Treatment on miRNA Expression During Experimental Liver Fibrosis
Presentation Date
7-2015
Abstract
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is an environmental contaminant that elicits toxicity through the aryl hydrocarbon receptor, although mechanisms of toxicity are poorly understood. We have previously found that exposure to TCDD exacerbates fibrogenesis in a mouse model of liver fibrosis. The goal of this project is to test the hypothesis that TCDD treatment increases liver damage through changes in microRNA (miRNA) expression. Male C57Bl/6 mice were treated for 8 weeks with carbon tetrachloride (CCl4) to induce liver fibrosis. TCDD (20 mg/kg) or peanut oil control was administered by gavage during the last 2 weeks of the experiment. Small RNAs were isolated from the liver, and miRNA expression is currently being analyzed by qPCR. We anticipate that increased fibrosis in TCDD-treated mice will coincide with increased expression of the profibrotic miRNAs miR-21 and miR-199, and decreased expression of miR-122 and miR-101a. Results from this project are expected to advance our understanding of the cellular and molecular mechanisms of TCDD toxicity.
Consequences of TCDD Treatment on miRNA Expression During Experimental Liver Fibrosis
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is an environmental contaminant that elicits toxicity through the aryl hydrocarbon receptor, although mechanisms of toxicity are poorly understood. We have previously found that exposure to TCDD exacerbates fibrogenesis in a mouse model of liver fibrosis. The goal of this project is to test the hypothesis that TCDD treatment increases liver damage through changes in microRNA (miRNA) expression. Male C57Bl/6 mice were treated for 8 weeks with carbon tetrachloride (CCl4) to induce liver fibrosis. TCDD (20 mg/kg) or peanut oil control was administered by gavage during the last 2 weeks of the experiment. Small RNAs were isolated from the liver, and miRNA expression is currently being analyzed by qPCR. We anticipate that increased fibrosis in TCDD-treated mice will coincide with increased expression of the profibrotic miRNAs miR-21 and miR-199, and decreased expression of miR-122 and miR-101a. Results from this project are expected to advance our understanding of the cellular and molecular mechanisms of TCDD toxicity.