Figure 4. CHOP is induced by fibrotic insult and promotes fibrosis.

(A) CCl₄ injection promotes collagen deposition. Masson's trichrome staining was used to assess collagen deposition (blue) in formalin-fixed paraffin-embedded liver sections of mice injected i.p. with 10% CCl₄ twice a week for 12 weeks, or with mineral oil as a control. (B–C) CHOP expression is associated with CCl₄-challenged livers. (B) CHOP was detected by IHC in mouse livers from (A) and samples were counterstained with hematoxylin as in Figure 1C. Representative data are shown. (C) The number of CHOP-positive nuclei per microscopic field from (B) was quantitated in multiple fields from 3 mice per group, and is expressed here as mean +/− S.E.M. per field. (D–E) Chop deletion attenuates DEN-induced fibrosis. Mild-to-moderate fibrosis is seen in wild-type but not Chop−/− livers by trichrome staining after DEN treatment as in Figure 2. Sections from two separate DEN-treated animals of each genotype are shown. (E) A METAVIR score was blindly determined from trichrome stains as described in the Materials and Methods, and the p-value was calculated by Asymptotic Wilcoxon Rank Sum Test. 0 = no fibrosis; 1 = portal fibrosis lacking septa; 2 = portal fibrosis with some septa; 3 = abundant septa; 4 = cirrhosis.