Three-dimensional structural analysis of ductular reaction and angiogenesis after liver injury

Abstract

The liver has a robust regenerative capacity, with different modes of regeneration according to the type and extent of injury. When the proliferation of hepatocytes is impaired as a result of hepatic injury, reactive bile ducts emerge and expand in the liver parenchyma, a process known as ductular reaction (DR). However, there is no information available about structural change of blood vessels in the liver when DR occurs. In this study, we analyzed the three-dimensional structure of bile ducts and blood vessels simultaneously using the tissue transparency technique. We show that angiogenesis occurs concurrently with DR in a mouse liver injury model. Inhibition of angiogenesis by the VEGFR-2 monoclonal antibody modulated the dynamics of blood vessels and biliary ducts. The findings of this study suggest that angiogenesis may play a role in the structural flexibility of DR.