TCDD Treatment Increases Expression of Delta-Like Homolog 1 (Dlk1) During Liver Fibrosis
Abstract
The aryl hydrocarbon receptor is a soluble, ligand-activated transcription factor that mediates the toxicity of environmental contaminants, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). We recently found that exposure to TCDD enhances liver fibrosis, which is a wound healing response mediated primarily by hepatic stellate cells. We investigated the possibility that TCDD increases the activation of hepatic stellate cells, by measuring the expression of delta-like 1 homolog (Dlk1), which is a soluble protein implicated in stellate cell activation. C57Bl/6 mice were treated with TCDD (20 µg/kg) or vehicle one day prior to bile duct ligation to induce hepatic fibrosis. Livers were harvested 3 and 7 days after surgery, RNA was isolated, and quantitative real-time PCR was performed. Dlk1 transcript levels were markedly elevated in the fibrotic liver of TCDD-treated mice as compared to control mice. This indicates that increased hepatic stellate cell activation may underlie the exacerbation of fibrosis in TCDD-treated mice and suggests that Dlk1 may be a previously unidentified AhR-regulated gene.