Targeted Modulation of Ah Receptor Activity to Inhibit Myofibroblast Activation
Abstract
Liver fibrosis is a wound healing response mediated by the activation of myofibroblast precursors, such as hepatic stellate cells. We recently found that myofibroblast activation is enhanced by exogenous activation of the aryl hydrocarbon receptor (AhR). The AhR is a ligand-activated transcription factor that mediates the toxicity of environmental pollutants, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Endogenous AhR activation also occurs and has been implicated in regulation of physiological processes, such as inflammation. Recently, a selective AhR modulator called SGA-360 was found to bind the AhR and suppress inflammation without exhibiting classical AhR agonist activity. The goal of this study was to determine if treatment with SGA-360 inhibits hepatic stellate cell activation. The LX-2 human hepatic stellate cell line was treated with TCDD or SGA-360, and cell proliferation was measured as an endpoint of activation. Results indicate that proliferation was altered in each treatment group, which provides a basis for further investigation into the therapeutic use of SGA 360 to modulate myofibroblast activation to enhance recovery from liver disease.