Figure 4.

Rho/MRTF pathway inhibitor CCG-222740 decreases the levels α-SMA in KC mice stimulated with caerulein. (A) Experimental design, n = 7 mice/cohort. Nine-week old KC mice were randomized into 2 groups: group A – caerulein injections (75 μg/kg) were administrated over 2 days, one injection every hour for 8 hours with an overnight rest; group B was treated daily for 7 days with CCG-222740 (100 mg/kg by oral gavage), starting 72 hours prior to the caerulein challenge. All mice were sacrificed 72 hours after the last caerulein injection, and blood, pancreas and spleen were collected. (B) α-SMA levels were evaluated by western blot of pancreas lysates. Representative blots are shown for 2 animals per cohort (−control; +treated). Quantitation of α-SMA blots included all animals enrolled in the study (6 mice/cohort), and values were expressed as fold induction compared to caerulein stimulated controls. Full blots shown in Supplemental Fig. 12. (C) Expression of α-SMA in cells was detected by immunohistochemistry (scale bar: 60 μm). Arrows indicate stellate cells. (D) MRTF levels were evaluated by western blot of pancreas lysates. Representative blots are shown for 2 animals per cohort. Quantitation of MRTF blots included all animals enrolled the study (5 mice/cohort), and values were expressed as fold induction compared to caerulein stimulated controls. Full blots are shown in Supplemental Fig. 12. (E) Expression of MRTF in cells was detected by immunohistochemistry (scale bar: 60 μm). *p < 0.05, Caerulein 75 μg/kg vs CCG-222740 treatment.