Kauma S, Hayes N, Weatherford S
Department of Obstetrics/Gynecology, Medical College of Virginia/Virginia Commonwealth University, Richmond 23298, USA.
J Clin Endocrinol Metab. 1997 Mar;82(3):949-54. doi: 10.1210/jcem.82.3.3806.
Met is the tyrosine kinase receptor for the ligand hepatocyte growth factor (HGF). Met/HGF plays an important role in epithelial cell proliferation, migration, and morphogenesis. HGF also plays a crucial role in placental development in the mouse. To determine whether HGF potentially has a similar role in human placental development, the production and localization of Met and HGF were determined in early second trimester and term placentas. Reverse transcription-PCR using specific primers demonstrated the expression of Met and HGF messenger ribonucleic acid in placental villi. HGF production was determined by enzyme-linked immunosorbent assay. HGF production over 48 h by second trimester placental villous explants in culture (810 pg/mg total protein x h) was 2.1-fold greater than that in term placental villous explants (380 pg/mg total protein x h; P < 0.01). Isolated trophoblast did not produce HGF, whereas isolated villous core tissues and villous core mesenchymal cells did produce HGF. Interleukin-1 beta treatment of placental villi or coculture of villous core mesenchymal cells with isolated trophoblast cells did not stimulate HGF production. Using immunohistochemistry, HGF localized to the villous core compartment with no localization to the trophoblast. In contrast, Met localized mainly to cytotrophoblast. These findings suggest that HGF produced by the villous core may act in a paracrine fashion to regulate trophoblast development or function through the HGF receptor, Met.
Met是配体肝细胞生长因子(HGF)的酪氨酸激酶受体。Met/HGF在上皮细胞增殖、迁移和形态发生中起重要作用。HGF在小鼠胎盘发育中也起着关键作用。为了确定HGF在人类胎盘发育中是否可能具有类似作用,我们测定了孕中期早期和足月胎盘组织中Met和HGF的产生及定位。使用特异性引物进行逆转录-聚合酶链反应(RT-PCR)证实了胎盘绒毛中Met和HGF信使核糖核酸的表达。通过酶联免疫吸附测定法测定HGF的产生。孕中期胎盘绒毛外植体在培养48小时内产生的HGF(810 pg/mg总蛋白×小时)比足月胎盘绒毛外植体(380 pg/mg总蛋白×小时;P<0.01)高2.1倍。分离的滋养层细胞不产生HGF,而分离的绒毛核心组织和绒毛核心间充质细胞确实产生HGF。白细胞介素-1β处理胎盘绒毛或绒毛核心间充质细胞与分离的滋养层细胞共培养均不刺激HGF的产生。使用免疫组织化学方法,HGF定位于绒毛核心区域,而不在滋养层细胞中定位。相比之下,Met主要定位于细胞滋养层。这些发现表明,绒毛核心产生的HGF可能以旁分泌方式通过HGF受体Met调节滋养层细胞的发育或功能。