Mutations in the SMAD2 gene have a relatively high occurrence in liver cancer, and overexpression of SMAD7 has been also reported in HCC patients.36 Indeed, the mutant Smads are degraded rapidly in comparison with their wild-type counterparts.37 Whereas the SMAD7 expression was not changed in gp130Δhepa compared with gp130f/f livers, SMAD2 protein expression was downregulated in the same experimental conditions (Figure 7d,Supplementary Figures 7e and f). Here, SMAD7 is linked to hepatocellular carcinoma.