Regulation of factors controlling angiogenesis in liver development: A role for PEDF in the formation and maintenance of normal vasculature

PEDF and VEGF are important inhibitors and promoters of angiogenesis, and the ratio between the two is an important indicator in many neovascular diseases. In mouse liver PEDF and VEGF ₁₆₅ were co-expressed at very early stages of liver development and their expression increased as liver embryogenesis progressed, suggesting that PEDF and VEGF are both crucial to vasculogenesis as well. VEGF ₁₈₉ only appears at the P0 stage in liver organogenesis and is maintained at high levels thereafter. PEDF and the two VEGF isoforms are synthesized by fresh and cultured hepatocytes. Expression of VEGF ₁₂₁ and overexpression of VEGF ₁₆₅ were only seen in HepG2, a well-characterized hepatocellular carcinoma line. The results suggest that hepatic vascular architecture is under the control of both PEDF and VEGF, and that VEGF ₁₆₅ and VEGF ₁₈₉ have distinct functions in normal vascular development of the liver. The VEGF isoforms 121 and 189 may be key regulators of increased vascularity and progression of hepatocellular carcinoma, one of the most common malignant tumors, and may be of prognostic significance for this tumor.