Role of the spleen in liver regeneration in relation to transforming growth factor-β1 and hepatocyte growth factor

Background: Optimizing the hepatic regenerative capacity is an immediate priority after partial hepatectomy (PH). Recent reports have indicated improvement in liver regeneration after splenectomy, raising interest on the role of the spleen in liver regeneration. However, little is known about the exact mechanism underlying these effects.

Materials and methods: Eight-week-old male Sprague-Dawley rats randomly underwent either 70% PH only (PH, n = 25) or 70% PH combined with splenectomy (PHS, n = 25). The specimens, including liver and/or spleen tissues and sera, were collected and evaluated using immunohistochemistry, Western blotting, enzyme-linked immunosorbent assay, and serum biochemical analyses.

Results: PH induced higher transforming growth factor (TGF)-β1 expression in the liver up to 72 h after PH. The PHS group showed significantly higher numbers of proliferating cell nuclear antigen-positive cells, reflecting higher liver regeneration and lower amounts of liver enzymes compared with the PH group. Splenectomy after PH resulted in increased and decreased serum concentrations of hepatocyte growth factor (HGF) and TGF-β1 in the portal vein, respectively. Moreover, the PHS group demonstrated downregulation of TGF-β1 and its receptor TGF-β-RII and upregulation of HGF and its receptor c-Met in the liver.

Conclusions: The spleen seemed to exhibit an inhibitory effect on liver regeneration by upregulating TGF-β1 and its receptor TGF-β-RII and downregulating HGF and its receptor c-Met in the liver. Therefore, splenectomy can be considered an option for improving liver regeneration in selected patients with reduced regenerative capacity of the liver.