Izumi S, Slayden O D, Rubin J S, Brenner R M
Division of Reproductive Sciences, Oregon Regional Primate Research Center, Beaverton 97006, USA.
Placenta. 1996 Mar-Apr;17(2-3):123-35. doi: 10.1016/s0143-4004(96)80005-1.
Keratinocyte growth factor (KGF) is synthesized and secreted exclusively by mesenchymal cells, and acts through its receptor (KGFR) to stimulate epithelial proliferation. In vivo, KGF and KGFR comprise a mesenchymal-epithelial cell paracrine system that can mediate epithelial cell mitosis. In preliminary work, we noted that KGF was expressed in the rhesus monkey placenta, and we now report on the expression of placental KGF and KGFR mRNAs during the course of gestation in this species. In-situ hybridization revealed that during early gestation, KGF mRNA was strongly expressed in placental mesenchymal cells. These cells, which were also immunoreactive for vimentin, were mainly located on the periphery of the mesenchymal cores of both anchoring and floating villi. KGFR mRNA was expressed in the adjacent trophoblastic epithelium, which was immunoreactive for cytokeratin. In-situ hybridization revealed that KGF mRNA expression was very high in the youngest placentae (34-days gestation) and decreased gradually to minimal levels by late gestation (157 days). Northern blot analysis indicated also that the KGF MRNA signal was strongest in early gestation samples and weakest by late gestation. Analysis for KGFR mRNA by a reverse transcriptase-polymerase chain reaction technique showed that KGFR mRNA expression could be detected at all stages. However, in-situ hybridization indicated that KGFR mRNA expression was highest in early gestation placentae and least in the oldest placentae. Autoradiographs of frozen sections of placenta that had been incubated with [125I]KGF to detect receptor binding showed that grain density over the trophoblast was highest in the youngest and least in the oldest placentae. PCNA and Ki-67 expression followed this same temporal trend. We conclude that the KGF/KGFR system may be important in proliferation of the placental trophoblast during early- to mid-pregnancy in rhesus monkeys.
角质形成细胞生长因子（KGF）仅由间充质细胞合成和分泌，并通过其受体（KGFR）发挥作用，以刺激上皮细胞增殖。在体内，KGF和KGFR构成一个间充质 - 上皮细胞旁分泌系统，可介导上皮细胞有丝分裂。在前期工作中，我们注意到KGF在恒河猴胎盘中表达，现在我们报告该物种妊娠期胎盘KGF和KGFR mRNA的表达情况。原位杂交显示，在妊娠早期，KGF mRNA在胎盘间充质细胞中强烈表达。这些细胞对波形蛋白也有免疫反应，主要位于固定绒毛和游离绒毛间充质核心的周边。KGFR mRNA在相邻的细胞角蛋白免疫反应性滋养层上皮中表达。原位杂交显示，KGF mRNA表达在最早期的胎盘（妊娠34天）中非常高，并在妊娠晚期（157天）逐渐降低至最低水平。Northern印迹分析也表明，KGF mRNA信号在妊娠早期样本中最强，在妊娠晚期最弱。通过逆转录 - 聚合酶链反应技术分析KGFR mRNA表明，在所有阶段均可检测到KGFR mRNA表达。然而，原位杂交表明，KGFR mRNA表达在妊娠早期胎盘最高，在最晚期胎盘最少。用[125I]KGF孵育胎盘冰冻切片以检测受体结合的放射自显影片显示，滋养层上的颗粒密度在最早期胎盘最高，在最晚期胎盘最少。增殖细胞核抗原（PCNA）和Ki - 67表达遵循相同的时间趋势。我们得出结论，KGF/KGFR系统可能在恒河猴妊娠早期至中期胎盘滋养层细胞的增殖中起重要作用。
