Fig. 1.

Recovery from liver injury and fibrosis. Panel A: Scheme of the experimental design. Mice were administered CCl₄ for 4 weeks to induce hepatic fibrosis as described in Materials and Methods. Animals were sacrificed 1, 3, 7, 14 and 28 days after cessation of CCl₄ to track fibrosis resolution. Panel B: Representative photos of livers and photomicrographs of stained liver sections are shown. Hematoxylin and eosin (H&E; 200 × ) shows general histology, while Sirius red brightfield (BF; 100 × ) and polarized light (PL; 100 × ) show fibrosis. Calibration bar for the photo is 1 cm. Calibration bars for the photomicrographs are 40 µm (200 × ) and 80 µm (100 × ). Panel C shows plasma transaminase (AST and ALT; IU/L) levels and hepatic mRNA expression of key indices of fibrosis (Col1a1, Acta2, Lox1, Lox2 and P4htm; Log2FC) are shown. Panel D shows representative zymographs demonstrating gelatin lysis by MMP-2 and −9. Panel E shows densitometric analysis of zymography (left; FC) and hepatic expression of key tissue inhibitors of metalloproteinases (Timp1, Timp2 and Timp3; right; Log2FC). Quantitative data are reported as box and whisker plots, which show the median (thick line), interquartile range (box) and range (whiskers) (n = 4–6). ^aP < 0.05 compared with absence of CCl₄ by 1-way repeated measures ANOVA using Bonferroni’s post hoc test. Groups surrounded by a box all are significantly different than control. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)