Yamane A, Seetharam L, Yamaguchi S, Gotoh N, Takahashi T, Neufeld G, Shibuya M
Department of Genetics, University of Tokyo, Japan.
Oncogene. 1994 Sep;9(9):2683-90.
Hepatocyte Growth Factor (HGF)/Scatter Factor secreted from sinusoidal endothelial cells and Kupffer cells in liver activates the c-Met tyrosine kinase receptor expressed on hepatocytes. Here we report yet another possible communication system through a different ligand and tyrosine kinase receptor in an opposite direction. We isolated and determined the primary structure of the entire coding region of rat flt-1 (fms-like tyrosine kinase), a receptor for Vascular Endothelial Growth Factor (VEGF). Using rat flt-1 cDNA as a probe we found that the flt-1 mRNA was expressed at very high levels in sinusoidal endothelial cells in normal rat liver, but was hardly detectable in hepatocytes. The transcripts of another VEGF receptor KDR/Flk-1 structurally related to Flt-1 was also expressed specifically in sinusoidal endothelial cells. On the other hand, VEGF mRNA was expressed weakly in hepatocytes, but not in the nonparenchymal cell fraction. Furthermore, in an in vitro culture system, VEGF demonstrated a remarkably specific growth-stimulatory activity as well as maintenance activity on the sinusoidal endothelial cells. These results suggest that hepatocytes regulate the proliferation and survival of the sinusoidal endothelial cells in liver in a paracrine manner. Therefore two reciprocal communication systems, VEGF-Flt receptor family and HGF-Met receptor, may exist in hepatic tissue.
肝血窦内皮细胞和肝 Kupffer 细胞分泌的肝细胞生长因子（HGF）/分散因子可激活肝细胞上表达的 c-Met 酪氨酸激酶受体。在此，我们报告了另一种可能的通讯系统，它通过不同的配体和酪氨酸激酶受体，作用方向相反。我们分离并确定了大鼠 flt-1（fms 样酪氨酸激酶）的整个编码区的一级结构，flt-1 是血管内皮生长因子（VEGF）的受体。用大鼠 flt-1 cDNA 作为探针，我们发现 flt-1 mRNA 在正常大鼠肝脏的肝血窦内皮细胞中高水平表达，但在肝细胞中几乎检测不到。另一种与 Flt-1 结构相关的 VEGF 受体 KDR/Flk-1 的转录本也特异性地在肝血窦内皮细胞中表达。另一方面，VEGF mRNA 在肝细胞中弱表达，但在非实质细胞部分不表达。此外，在体外培养系统中，VEGF 对肝血窦内皮细胞表现出显著的特异性生长刺激活性以及维持活性。这些结果表明，肝细胞以旁分泌方式调节肝脏中肝血窦内皮细胞的增殖和存活。因此，肝组织中可能存在两个相互的通讯系统，即 VEGF-Flt 受体家族和 HGF-Met 受体。
