Kataoka H, Meng J Y, Itoh H, Hamasuna R, Shimomura T, Suganuma T, Koono M
Second Department of Pathology, Miyazaki Medical College, Kiyotake, Japan.
Histochem Cell Biol. 2000 Dec;114(6):469-75. doi: 10.1007/s004180000228.
Activation of hepatocyte growth factor (HGF) is a crucial limiting step in HGF-induced signaling pathway. The HGF activator inhibitor type 1 (HAI-1) was identified as a potent inhibitor of HGF activator (HGFA), a serine proteinase that is responsible for the activation of HGF in vivo. HAI-1 is an integral membrane Kunitz-type serine proteinase inhibitor, and its mRNA has been reported to be most abundant in the placenta. In this report, specific antibody to HAI-1 was used in an immunohistochemical procedure to determine the localization of HAI-I in human placenta. HAI-1 was expressed in cytotrophoblasts (Langhans' cells) of the double-layered trophoblastic epithelium of chorionic villi tissue, and syncytiotrophoblasts were almost negative. On the other hand, extravillous trophoblasts of cytotrophoblastic columns showed markedly decreased immunoreactivity, and those infiltrating into the superficial decidua membrane of early placenta were hardly stainable. The amnionic epithelial cells were also immunostained intensely. The presence of HAI-1 mRNA was also confirmed in a cultured human cytotrophoblastic cell line. In addition to HAI-1, low but distinct expression of HGFA mRNA was observed in the placenta tissue and cultured cytotrophoblasts by using a sensitive RT-PCR method. Since HGF plays an essential role in the placenta development, expression of HAI-1 and HGFA may have an important regulatory role in the placenta. The localization of HAI-I in the proliferating trophoblastic stem cells (Langhans' cells), but not in syncytiotrophoblasts and extravillous trophoblasts, suggest a possible role of HAI-1 in the proliferation of trophoblasts.
肝细胞生长因子（HGF）的激活是HGF诱导信号通路中的一个关键限速步骤。HGF激活剂抑制剂1型（HAI-1）被鉴定为HGF激活剂（HGFA）的有效抑制剂，HGFA是一种丝氨酸蛋白酶，负责在体内激活HGF。HAI-1是一种整合膜Kunitz型丝氨酸蛋白酶抑制剂，据报道其mRNA在胎盘中最为丰富。在本报告中，HAI-1特异性抗体用于免疫组织化学程序，以确定HAI-1在人胎盘中的定位。HAI-1在绒毛膜绒毛组织双层滋养层上皮的细胞滋养层（朗汉斯细胞）中表达，而合体滋养层几乎呈阴性。另一方面，细胞滋养层柱的绒毛外滋养层显示免疫反应性明显降低，而那些浸润到早期胎盘浅表蜕膜的细胞几乎无法染色。羊膜上皮细胞也被强烈免疫染色。在培养的人细胞滋养层细胞系中也证实了HAI-1 mRNA的存在。除了HAI-1，通过使用灵敏的逆转录聚合酶链反应（RT-PCR）方法，在胎盘组织和培养的细胞滋养层中观察到HGFA mRNA的低但明显的表达。由于HGF在胎盘发育中起重要作用，HAI-1和HGFA的表达可能在胎盘中具有重要的调节作用。HAI-1在增殖的滋养层干细胞（朗汉斯细胞）中定位，但不在合体滋养层和绒毛外滋养层中定位，这表明HAI-1在滋养层增殖中可能发挥作用。
