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Analysis of Lgr4 function and development of anti-LGR4 antibody drug in gynecology

Lgr4功能分析及妇科抗LGR4抗体药物开发

基本信息

批准号：
24659732
负责人：
KOIZUMI MASAE
金额：
$ 2.33万
依托单位：
Ehime University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Challenging Exploratory Research
财政年份：
2012
资助国家：
日本
起止时间：
2012-04-01 至 2014-03-31
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-24659732/
关键词：
性分化雌生殖器分化 Lgr4

项目摘要

Leucine-rich repeat-containing G-protein coupled receptor 4 (LGR4) is a type of membrane receptor with a seven-transmembrane structure.We observed that Lgr4-/- female mice showed abnormal development of the Wolffian ducts, the appearance of male-like somatic cells in the ovaries. Lgr4-/- female mice exhibited masculinization similar to RSPO1-, beta-catenin-, and Wnt4-deficient mice. In the Lgr4-/- ovarian somatic cells, Lefl and Axin2 expression was reduced, which were target genes of Wnt-beta catenin signaling. On the other hand the androgen receptor (AR) expression in Wolffian ducts and ovarian somatic cells of Lgr4-/- female was increased. This study suggested that Lgr4 was critical to ovarian somatic cell specialization through the cooperative signaling of RSPOs and Wnt and involved the regulation of the AR expression in female reproductive organs.

富含亮氨酸重复序列的G蛋白偶联受体4（LGR4）是一种具有七次跨膜结构的膜受体。我们观察到Lgr4-/-雌性小鼠的沃尔夫管发育异常，卵巢中出现类似雄性的体细胞。 Lgr4-/- 雌性小鼠表现出与 RSPO1-、β-连环蛋白-和 Wnt4 缺陷小鼠相似的雄性化。在Lgr4-/-卵巢体细胞中，Wnt-β连环蛋白信号传导的靶基因Lefl和Axin2表达降低。另一方面，Lgr4-/-雌性的沃尔夫管和卵巢体细胞中雄激素受体(AR)的表达增加。这项研究表明，Lgr4 通过 RSPO 和 Wnt 的协同信号传导对卵巢体细胞特化至关重要，并参与女性生殖器官中 AR 表达的调节。