Cadherin-11 contributes to liver fibrosis induced by carbon tetrachloride

Background and aims

Liver fibrosis is characterized by the excessive deposition of extracellular matrix (ECM) leading to impaired function and cirrhosis. Previous reports support a role for cadherin-11 (CDH11) in regulating the development of dermal and pulmonary fibrosis. In the current report, the extent to which CDH11 modulates the development of liver fibrosis induced by carbon tetrachloride (CCL₄) was assessed.

Methods

Wild type (WT) and CDH11 deficient (CDH11^-/-) mice were treated with CCl₄ or vehicle control for 8 weeks to induce liver fibrosis. Liver fibrosis was assessed by histology, collagen content, and RTPCR of fibrotic mediators.

Results

Livers from WT mice treated with CCl₄ had increased levels of CDH11 which localized to injured hepatocytes, hepatic stellate cells, and macrophages. Interestingly, CDH11^-/- mice had decreased histological evidence of liver fibrosis, collagen deposition, α-smooth muscle actin (α-SMA) accumulation, and mRNA levels of fibrotic mediators such as Col1-α1, Snail, TGF-β and IL-6.

Conclusions

These data demonstrate that CDH11 is increased during liver fibrosis, is an important regulator of liver fibrosis induced by CCL₄ and suggest that CDH11 may be a potential therapeutic target for liver fibrosis.