Ishikawa K S, Masui T, Ishikawa K, Shiojiri N
Department of Biology, Faculty of Science, Shizuoka University, Oya 836, Shizuoka 422-8529, Japan.
Histochem Cell Biol. 2001 Nov;116(5):453-62. doi: 10.1007/s00418-001-0342-6. Epub 2001 Nov 9.
Although hepatocyte growth factor (HGF) was discovered as a potent hepatotrophic factor responsible for liver regeneration and may involve some organ development in embryogenesis, it remains to be revealed what roles HGF plays in liver development. The present study was undertaken to determine which cells express HGF and its receptor c-Met and when c-Met is activated in mouse liver development by using immunoblotting and immunohistochemical techniques. HGF was detected in hepatocytes and non-parenchymal cells, including biliary epithelial cells, periportal connective tissue cells, megakaryocytes, endothelial cells, and sinusoidal cells, throughout liver development. Positive HGF immunostaining in hepatocytes increased during postnatal development, and reached the maximal level in the adult stage. c-Met protein was also expressed in hepatocytes throughout liver development, but maximal staining was obtained in 1- or 2-week-old livers. Phosphorylation of tyrosine residues in the c-Met beta chain also occurred in these stages. These results suggest that HGF signaling is implicated in hepatocyte growth during postnatal liver development, and its action could be in a paracrine mode; HGF produced by non-parenchymal cells such as sinusoidal cells acts on hepatocytes expressing c-Met receptors. Positive immunostaining in adult and postnatal hepatocytes may be derived from their blood clearance of HGF.
尽管肝细胞生长因子（HGF）作为一种负责肝脏再生的强效肝营养因子被发现，并且可能在胚胎发育中参与一些器官的发育，但HGF在肝脏发育中发挥何种作用仍有待揭示。本研究旨在通过免疫印迹和免疫组织化学技术，确定在小鼠肝脏发育过程中哪些细胞表达HGF及其受体c-Met，以及c-Met何时被激活。在整个肝脏发育过程中，在肝细胞和非实质细胞中均检测到HGF，这些非实质细胞包括胆管上皮细胞、门静脉周围结缔组织细胞、巨核细胞、内皮细胞和肝血窦细胞。肝细胞中HGF免疫染色阳性在出生后发育过程中增加，并在成年期达到最高水平。c-Met蛋白在整个肝脏发育过程中也在肝细胞中表达，但在1至2周龄的肝脏中获得最大染色。c-Metβ链中酪氨酸残基的磷酸化也发生在这些阶段。这些结果表明，HGF信号传导与出生后肝脏发育过程中的肝细胞生长有关，其作用可能以旁分泌模式进行；由肝血窦细胞等非实质细胞产生的HGF作用于表达c-Met受体的肝细胞。成年和出生后肝细胞中的阳性免疫染色可能源于它们对HGF 的血液清除。
