Figure 6.

Cartoon depicting disparate modes of repair after long-term DDC-exposure in WT and TG livers. Although bidirectional repair from surviving bile ducts and hepatocytes ensures survival after chronic DDC injury that induces biliary and hepatocyte damage, the predominant mechanism seems to be through ductular proliferation, oval cell activation, and transdifferentiation to hepatocytes in WT livers. In TG livers, however, increased numbers of A6- and AFP-positive atypical hepatocytes panzonally and lack of periportal retention of biliary markers indicate enhanced transdifferentiation of β-catenin transgene-expressing hepatocytes to the biliary phenotype, eventually resolving intrahepatic cholestasis. An alternate scenario of increased differentiation to biliary cells and “spillover” to form A6-positive hepatocytes on expression of β-catenin transgene in oval cells may also contribute to the resolution of biliary injury.