Inhibitory effects of 1,7-dimethylxanthine (paraxanthine) on TGF-beta (Smad2/3) signaling in transdifferentiating rat hepatic stellate cells

Background and Aim: Based on reports of a hepatoprotective effect of coffee consumption, we were the first to give evidence that caffeine suppresses TGF-β dependent Smad signaling and target gene (e.g. CTGF) induction in hepatocytes. Ongoing investigations finally identified the primary caffeine metabolite paraxanthine (1,7-dimethylxanthine; 1,7-DMX) as the most potent xanthine-derived inhibitor of TGF-β signaling in PC, but its effect on TGF-β signaling in hepatic stellate cells (HSC) was not yet investigated. Methods: HSC were isolated by the pronase-collagenase perfusion technique, and treated with different…