Mice expressing the RSK-inhibitory C/EBPβ-Ala217 transgene are refractory to the induction of liver fibrosis.

C/EBPβ^+/+ [wt], C/EBPβ-Ala217 and C/EBPβ^−/− [ko] mice received weekly IP injections of CCl₄ or mineral oil (control) for 12 weeks as described in Methods. A. Representative Mallory's trichrome stain for liver fibrosis (in blue; arrowheads). All C/EBPβ^+/+ (wt) mice (n: 12) developed severe liver fibrosis. The C/EBPβ-Ala217 (n: 12; P<0.0001) and C/EBPβ^−/− [ko] (n: 6; P<0.01) mice had either no fibrosis or only minimal liver fibrosis. B. Representative Sirius red immunohistochemistry for collagen (in red; arrowhead). Marked increase in liver collagen in a cirrhotic pattern was observed in C/EBPβ^+/+, but not in C/EBPβ-Ala 217 or C/EBPβ^−/− [ko], mice. C. Analysis of hepatic collagen content by the Sirius red collagen–binding assay, showed a ∼2.5-fold increase in C/EBPβ^+/+ mice treated with CCl₄ (n: 12), compared to C/EBPβ-Ala217 mice treated with CCl₄ (n: 12; P<0.001). C/EBPβ^−/− mice were also refractory to the induction of liver fibrosis by CCl₄ (n: 6; P<0.01). D. Analysis of hepatic collagen content by the hydroxyproline assay, showed a ∼2-fold increase in C/EBPβ^+/+ mice treated with CCl₄ (n: 7), compared to C/EBPβ-Ala217 mice treated with CCl₄ (n: 6; P<0.01). C/EBPβ^−/− mice were also refractory to the induction of liver fibrosis by CCl₄ (n: 6; P<0.01).