Fibrosis.

<p>Fibrosis scoring: α-SMA (hepatic stellate cell activation) and reticulin grading (collagen type III) in five COMMD1-deficient dogs in a time-dependent copper-induced hepatitis. Data are presented as median (range).</p><p>α-SMA grading; 0: no staining of HSCs; 1: a few positive HSCs; 2: diffuse staining of HSCs; 3: mild increased staining of HSCs; 4: marked increased staining of HSC and compared with age matches normal controls.</p><p>Reticulin grading; grade 0: normal, grade 1: local mild centrilobular increase, grade 2: multifocal mild to moderate centrilobular increase, grade 3: moderate increase with centro-central bridging or nodular transformation. The uncorrected p-values for comparison of each time point with 6 months of age are reported in the table. No significant differences are present when correcting these p-values for the number of tests.</p

Blood examinations.

<p>ALT: alanine aminotransferase; AP: alkaline phosphatase.</p><p>Blood examinations during aging in five COMMD1-deficient dogs. Values are expressed as median (range).</p>*<p>significantly increased serum concentration compared with 12 months of age.</p

TGF-β1 pathway.

<p>(<b>A</b>) Gene-expression profiling. Interaction plots of Q-PCR data of important mediators of fibrogenesis in a time-dependent copper-induced hepatitis in five COMMD1-deficient dogs. Q-PCR results were normalized against the expression of six control dogs (one to three years of age). Linear mixed-effect modeling was used; * significant difference corrected for multiple testing. (<b>B</b>) Western blot analysis on the activation of TGF-beta signalling (total Smad2 and phosphorylated Smad2 (Ser727)) of five COMMD1-deficient dogs at 12, 30, and 42 months. β-actin (ACTB) served as loading control.</p

Histological description.

<p>COMMD1-deficient dog livers were stained with H&E and RA to assess inflammation and copper accumulation, respectively, and stained for α-SMA and reticulin (collagen type III) to assess fibrosis. Representative pictures of a COMMD1-deficient dog over a period of 42 months are shown. Numbers indicate age in months.</p

HGF pathway.

<p>(<b>A</b>) Gene-expression profiling. Interaction plots of Q-PCR data of important mediators of regeneration in a time-dependent copper-induced hepatitis in five COMMD1-deficient dogs. Q-PCR results were normalized against the expression of six control dogs (one to three years of age). Linear mixed-effect modeling was used; * significant difference corrected for multiple testing. (B) Western blot analysis on the activation HGF-signalling (HGF, phosphorylated c-Met, (phosphorylated) STAT3) of five COMMD1-deficient dogs at 12, 30, and 42 months. β-actin (ACTB) served as loading control.</p