Significance of Portal Venous VEGF During Liver Regeneration After Hepatectomy

Background

Although some studies have hypothesized portal venous blood is important for liver regeneration, no studies have established organs whose venous effluent flow into the portal vein secrete liver regenerating factors into the portal vein during liver regeneration. The aim of this study was to elucidate up-regulation of vascular endothelial growth factor (VEGF) in the portal vein, and expressions of hepatic regenerating factors in organs whose venous effluent flows into the portal vein during liver regeneration.

Materials and Methods

VEGF protein in systemic and portal venous blood, as well as expression of VEGF, hypoxia-inducible factor-1alfa (HIF-1α), hepatocyte growth factor (HGF), and HGF activator (HGFA) mRNA were evaluated in the regenerating liver, spleen, and intestine following 70% partial hepatectomy (PHx) in rats.

Results

The portal VEGF protein level was significantly higher than the systemic level post-PHx (portal/systemic at 72, 120, and 168 h post-PHx: 17.2/13.0, 20.2/12.8, and 24.0/14.7 pg/mL; P = 0.003, P = 0.022 and P = 0.032, respectively). VEGF mRNA expressions were significantly higher in the liver (P = 0.000027: 168 h), spleen (P = 0.000059: 72 h) and intestine (P = 0.01: 24–72 h) post-PHx compared with pre-PHx. HIF-1α, HGF, and HGFA mRNA expressions in the liver, intestine, and spleen were also significantly higher post-PHx compared to pre-PHx.

Conclusions

Portal VEGF was significantly higher than systemic VEGF, and expressions of VEGF, HIF-1α, HGF, and HGFA mRNA in the liver, spleen and intestine were also up-regulated during liver regeneration. These results suggest that hepatic regenerating factors derived from the spleen or intestine may contribute liver regeneration.

Key Words: liver regeneration, portal vein, VEGF, HIF-1α, HGF, HGFA, spleen, intestine, partial hepatectomy