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

2007-12-26T00:01:00Z (GMT) by Martina Buck Mario Chojkier

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).