Increased expressions of vascular endothelial growth factor and its receptors, flt-1 and KDR/flk-1, in regenerating rat liver

Sinusoidal endothelial cells proliferate following hepatocyte regeneration in the liver after partial resection. The expressions of vascular endothelial growth factor (VEGF) and its receptors, flt-1 and KDR/flk-1, were studied by Northern blotting in isolated rat liver cells and 70% resected rat liver. VEGF was expressed in hepatocytes immediately after isolation, and both flt-1 and KDR/flk-1 were expressed in non-parenchymal cells including sinusoidal endothelial cells. The VEGF expression in hepatocytes decreased during primary culture for 48 hr. This expression was maintained at 48 hr of culture by addition of EGF to the medium at 24 hr, increasing thereafter. VEGF, flt-1, and KDR/flk-1 were also expressed in normal rat liver. In 70% resected rat liver, VEGF expression increased with a peak at 72 hr after the operation, followed by expressions of flt-1 and KDR/flk-1 increasing between 72 and 168 hr. These results suggest that VEGF expression increases in regenerating hepatocytes, which may contribute to proliferation of sinusoidal endothelial cells of rat liver following partial resection, probably through flt-1 and KDR/flk-1 receptors upregulated on sinusoidal endothelial cells. (C) 1996 Academic Press, Inc.