Functional analysis of LH/hCG receptor in human placental chorionic villous macrophages

人胎盘绒毛膜绒毛巨噬细胞LH/hCG受体的功能分析

• 批准号: 15591763
• 负责人: KATABUCHI Hidetaka
• 金额: $ 2.24万
• 依托单位: Kumamoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15591763/
• 关键词: Placenta; Villi; Macrophage; LH-hCG receptor; exon 9-deleted LH-hCG receptor; THP-1 cell; hCG; hCG β subunit core fragment; hCGβ subunit core fragment; hCG β subunit core fragment; hCGβsubunit core fragment

Human gonads and non-gonadal organs/tissues express LH/CG receptors. This study aimed to identify the LH/CG receptors and to clarify their function in human placental chorionic villous macrophages. Macrophages as well as syncytiotrophoblasts of human chorionic villous tissues were immunohistochemically positive for LH/CG receptor throughout gestation. By RT-PCR, villous macrophages were shown to express a variant type of LH/CG receptor, the sequencing of which revealed a deletion of exon 9. For experiments in vitro, a monocyte-macrophage cell line, THP-1, was transfected with vector alone, wild-type LH/CG receptor, and exon 9-deleted LH/CG receptor after phorbol 12-myristate 13-acetate (PMA) treatment. Non-PMA-treated THP-1 cells transfected with vector alone were also examined. THP-1 cells expressed exon 9-deleted LH/CG receptor after treatment with PMA. After the cells of the four groups were cultured in medium containing intact hCG, the concentrations of hCG and its b-core fragment … More (β-CF) were measured in the supernatant of the culture medium and in the cell cytosol. Time-dependent hCG uptake was observed in both non-PMA-treated and PMA-treated THP-1 cells, suggesting that the variant receptor is not directly involved in the ingestion of hCG. The degradation of hCG and excretion of β-CF were progressed in PMA-treated cells but not in the un-treated cells. In the cell cytosol, the ratio of β-CF and hCG concentrations (β-CF/hCG) was significantly higher in the PMA-treated cells than in non-PMA-treated cells ; however, it did not differ between the PMA-treated cells transfected with exon 9-deleted receptor and those transfected with vector alone. Macrophages may express the variant receptor in order to recognize the intracytoplasmic hCG and transport it to the lysosome. Among the two PMA-treated cells, the ratio was lower in those transfected with wild-type receptor. The expression of the variant receptor may modulate the degradation of hCG but be reduced by expression of the wild-type receptor in its lacking macrophages. Our data suggest a potentially important role for exon 9-deleted LH/CG receptors expressed in human placental villous macrophages in the local metabolism of hCG. Less

人类性腺和非性腺器官/组织表达LH/CG受体。本研究旨在鉴定人胎盘绒毛膜绒毛巨噬细胞中LH/CG受体并阐明其功能。人绒毛膜绒毛组织巨噬细胞和合体滋养细胞在整个妊娠期LH/CG受体免疫组化阳性。通过RT-PCR，绒毛巨噬细胞表达一种LH/CG受体的变异类型，其测序显示外显子9缺失。在体外实验中，将载体、野生型LH/CG受体和外显子9缺失的LH/CG受体分别转染单核巨噬细胞系THP-1，经phorbol 12-肉豆汁酸13-乙酸酯（PMA）处理。用载体单独转染未经pma处理的THP-1细胞也进行了检测。经PMA处理后，THP-1细胞表达外显子9缺失的LH/CG受体。四组细胞在含完整hCG的培养基中培养后，测定培养基上清液和细胞质中hCG及其b核片段β-CF的浓度。在非pma处理和pma处理的THP-1细胞中都观察到hCG摄取的时间依赖性，这表明变异受体不直接参与hCG的摄取。在pma处理的细胞中，hCG的降解和β-CF的排泄有进展，而在未处理的细胞中没有进展。在细胞质中，pma处理的细胞β-CF和hCG浓度之比（β-CF/hCG）显著高于未处理的细胞；然而，转染外显子9缺失受体的pma处理细胞与单独转染载体的细胞之间没有差异。巨噬细胞表达这种变异受体是为了识别胞浆内hCG并将其转运到溶酶体。在两种pma处理的细胞中，转染野生型受体的细胞比例较低。变异受体的表达可以调节hCG的降解，但在其缺失的巨噬细胞中，野生型受体的表达会减少hCG的降解。我们的数据表明，在人胎盘绒毛巨噬细胞中表达的外显子9缺失的LH/CG受体在hCG的局部代谢中具有潜在的重要作用。少

项目成果

Expression of variant luteinizing hormone/chorionic gonadotropin receptors and degradation of chorionic gonadotropin in human chorionic villous macrophages.

• DOI: 10.1016/j.placenta.2004.07.001
• 发表时间: 2005-04
• 期刊: Placenta
• 影响因子: 3.8
• 作者: N. Sonoda;H. Katabuchi;H. Tashiro;T. Ohba;R. Nishimura;T. Minegishi;H. Okamura

Establishment of an immortalised human ovarian surface epithelial cell line without chromosomal instability

• DOI: 10.1038/sj.bjc.6602662
• 发表时间: 2005-07-11
• 期刊: BRITISH JOURNAL OF CANCER
• 影响因子: 8.8
• 作者: Maeda, T;Tashiro, H;Okamura, H
• 通讯作者: Okamura, H

Pathophysiological dynamics of human ovarian surface epithelial cells in epithelial ovarian carcinogenesis, review

人卵巢表面上皮细胞在卵巢上皮癌发生中的病理生理动力学，综述

• 发表时间: 2005
• 期刊: International review of cytology 242
• 作者: Okamura H.;Katabuchi H.
• 通讯作者: Katabuchi H.

N.Sageshima, et al.: "Necrotic feature of the trophoblasts lacking HLA-G expression in normal and preeclamptic placentas"American Journal of Reproductive Immunology. 49. 174-182 (2003)

N.Sageshima 等人：“正常和先兆子痫胎盘中缺乏 HLA-G 表达的滋养层细胞的坏死特征”美国生殖免疫学杂志。

Histologic type, organ of origin, and Wnt pathway status: effect on gene expression in ovarian and uterine carcinomas.

组织学类型、起源器官和 Wnt 通路状态：对卵巢癌和子宫癌基因表达的影响。

• DOI: 10.1158/1078-0432.ccr-04-2061
• 发表时间: 2005
• 期刊: Clinical cancer research : an official journal of the American Association for Cancer Research.
• 作者: Shedden,KerbyA;Kshirsagar,MaltiP;Schwartz,DonaldR;Wu,Rong;Yu,Hongfeng;Misek,DavidE;Hanash,Samir;Katabuchi,Hidetaka;Ellenson,LoraHedrick;Fearon,EricR;Cho,KathleenR
• 通讯作者: Cho,KathleenR