Changes of Endocan and its effect on hepatic stem cells during the rapid proliferation process of residual liver after ALPPS procedure.

Abstract

To establish a stable animal model of associating liver partition and portal vein ligation for staged hepatectomy (ALPPS), as well as to explore whether Endocan and HGF/c-Met signalling pathway participate in the regeneration of residual liver through hepatic stem cells after ALPPS procedure. C57BL/6J male mice weighing 18-22 g were used in this study. The liver regeneration index was expressed as the ratio of Future Liver Remnant (FLR)/Body weight (BW) × 100%. Expression of hepatic stem cell marker CK19 was assessed by immunohistochemical method. Serum levels of vascular endothelial growth factor (VEGF) and Endocan were detected by ELISA. VEGF, Endocan and c-Met contents in residual liver were observed by Western blot analysis. The expression levels of Endocan and HGF/c-Met pathway-related genes were evaluated by qRT-PCR. Compared with the portal vein ligation (PVL) group and sham group, the ALPPS group had more CK19 positive cells and a higher liver regeneration index (P < .05). The serum levels of VEGF in the ALPPS group were increased significantly (P < .05) from the first day and decreased from the second day after surgery, and maintained consistently higher than that of the sham group (P < .05). Western blot showed that the expressions of VEGF and Endocan in ALPPS group were significantly higher than those in both sham and PVL groups at different time points. The Endocan plays a role in the rapid regeneration of residual liver after ALPPS, likely through the interaction with the HGF/c-Met pathway to affect the hepatic stem cell population. SIGNIFICANCE OF THE STUDY: Our animal study provides valuable insights on the effect of Endocan in the process of rapid regeneration of residual liver after ALPPS, which would lead to the possible expansion of clinical research on ALPPS surgery and further studies on its molecular underpinning during liver regeneration.