Vismodegib Suppresses TRAIL-mediated Liver Injury in a Mouse Model of Nonalcoholic Steatohepatitis (original) (raw)
Figure 4
Vismodegib abrogates FFC diet-induced upregulation of death receptor DR5 and prevents DR5-mediated liver injury in FFC diet-fed mice.
(A, B) Mice were fed chow or the FFC diet for 3 months. Mice were then treated with vismodegib or vehicle for an additional week prior to sacrifice. Total RNA was extracted from the liver tissue and expression of death receptors (A) and death receptor ligands (B) was quantified by real-time PCR. (C, D) A subset of mice were reared on either chow or FFC diet for 3 months and then treated with vismodegib or vehicle for 2 weeks. Two injections of MD5-1, an agonistic anti-DR5 antibody, were administered to vismodegib- and vehicle-treated groups on each diet during the last week prior to sacrifice. Serum ALT values (C) and liver TUNEL-positive cells (D) were analyzed in all groups. (E) Huh-7 cells were pre-treated with vismodegib (0–1 µM) for 16 h and then treated with 600 µM palmitic acid (PA) for additional 8 h. Total RNA was extracted and DR5 expression was evaluated by real-time PCR. DR5 expression in Huh-7 cells is expressed as mean values of four independent experiments. Data represent mean ± S.E.M. *** P<0.001, ** P<0.05, * P<0.01.