Recovery of Liver Sinusoidal Endothelial Cells Following Monocrotaline-induced Liver Injury.

Abstract

Although the pathology of sinusoidal obstruction syndrome (SOS) is characterized by damage to liver sinusoidal endothelial cells (LSECs), the processes underlying LSEC repair are incompletely understood. The angiopoietin (Ang)/Tie system contributes to angiogenesis. The present study aimed to examine the processes of LSEC repair and the involvement of the Ang/Tie pathway in LSEC recovery. Experimentally, SOS was induced by intraperitoneal injection of monocrotaline (MCT) to C57/BL6 mice. Levels of LSEC markers were up-regulated during the repair phase of MCT-induced hepatotoxicity. The damaged LSECs recovered from the injury by expanding LSECs expressing lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1) in the peri-central area of MCT-injured livers, while LSECs in the same area of uninjured livers lacked LYVE-1 expression. Bone marrow (BM)-derived cells did not incorporate into the restored LSECs. Tie2 expression was related to LSEC recovery in MCT-injured liver tissue. The resident LSECs neighboring uninjured tissue replace damaged LSECs in MCT-injured livers. Tie2 is involved in LSEC recovery from MCT-induced hepatotoxicity.