Treatment with the novel allosteric αM β2 integrin activator LA-1 reduces fibrosis in livers of WT mice with established periductal fibrosis. WT mice were fed a control diet (AIN-93M) or an identical diet containing 0.025% ANIT for 6 weeks. Mice were treated with vehicle (1.5 μL DMSO in 100 μL sterile PBS) or LA-1 twice daily (0.4 mg/kg per day, IP) in weeks 5 and 6. (A) CK-19 staining and (B) sirius red staining were quantified as described in “Methods.” (C) Serum ALT activity determined was as described in “Methods.” Hepatic expression of mRNAs encoding the genes: (D) NOS2, (E) TGFβ2, (F) COL1A1, and (G) ITGβ6 was determined by real-time qPCR. Data are expressed as mean + SEM; mice fed the control diet (n = 5) and mice fed the ANIT diet (n = 12 to 13 mice per group). *P < .05 vs respective treatment on control diet; #P < .05 vs vehicle-treated ANIT-exposed mice. Veh, vehicle.
