Physiological role of lysophosphatidic acid.

溶血磷脂酸的生理作用。

• 批准号: 15370052
• 负责人: AOKI Junken
• 金额: $ 9.86万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15370052/
• 关键词: lysophosphatidic acid; LPA3; implantation; knockout mice; prostaglandin; リゾホスファチジン酸受容体; オートタキシン; autotaxin; がん; 浸潤・転移

Every successful pregnancy requires proper embryo implantation. (a process of particular importance) Poor implantation rate is a major problem during infertility treatments using assisted reproductive technologies (ART). We report a new molecular influence on implantation through the lysophosphatidic acid (LPA) receptor LPA_3/edg7. Targeted deletion of LPA_3 resulted in significantly reduced litter size, which could be attributed to delayed implantation and altered embryo spacing. These two events led to embryo death or delayed embryonic development and hypertrophic placentas shared by multiple embryos. An enzyme demonstrated to influence implantation, cyclooxygenase-2 (COX-2), was down-regulated in LPA_3-deficient uteri during preimplantation. COX-2 produces prostaglandins that are critical for implantation ^1, and exogenous administration of the prostaglandins PGE_2 and cPGI into LPA_3-deficient females rescued delayed implantation but did not rescue defects in embryo spacing. These data identify LPA_3 receptor-mediated signaling as a new influence on implantation and further indicate linkage between LPA signalling and prostaglandin biosynthesis.

每次成功怀孕都需要适当的胚胎植入。 （一个特别重要的过程）植入率低是使用辅助生殖技术（ART）治疗不孕症的一个主要问题。我们报告了通过溶血磷脂酸 (LPA) 受体 LPA_3/edg7 对植入的新分子影响。 LPA_3 的靶向删除导致窝产仔数显着减少，这可能归因于植入延迟和胚胎间距改变。这两个事件导致胚胎死亡或胚胎发育延迟以及多个胚胎共享的胎盘肥大。一种被证明会影响着床的酶——环氧合酶-2 (COX-2)，在植入前在 LPA_3 缺陷的子宫中被下调。 COX-2 产生对着床至关重要的前列腺素^1，并且将前列腺素 PGE_2 和 cPGI 外源性给予 LPA_3 缺陷的雌性可挽救延迟着床，但不能挽救胚胎间隔缺陷。这些数据将 LPA_3 受体介导的信号传导确定为对植入的新影响，并进一步表明 LPA 信号传导与前列腺素生物合成之间的联系。

项目成果

Type II platelet-activating factor-acetylhydrolase is essential for epithelial morphogenesis in C. elegans

II 型血小板激活因子乙酰水解酶对于秀丽隐杆线虫上皮形态发生至关重要

• 发表时间: 2004
• 期刊: Proc.Natl.Acad.Sci.USA 101
• 作者: F.Bonin;S.D.Ryan;L.Migahed;F.Mo;J.Lallier;D.J.Franks;H.Arai;S.A.L.Bennett;T.Inoue et al.
• 通讯作者: T.Inoue et al.

LPA 3-mediated lysophosphatidic acid signalling in implantation and embryo spacing

• 发表时间: 2008
• 作者: X. Ye;K. Hama;J. Contos;B. Anliker;A. Inoue;Michael;K. Skinner;Hiroshi Suzuki;T. Amano;Grace Kennedy;H. Arai;Junken;Aoki;J. Chun

Prostatic acid phosphatase degrades lysophosphatidic acid in seminal plasma

• DOI: 10.1016/j.febslet.2004.06.083
• 发表时间: 2004-07-30
• 期刊: FEBS LETTERS
• 影响因子: 3.5
• 作者: Tanaka, M;Kishi, Y;Arai, H
• 通讯作者: Arai, H

Lysophosphatidic acid and autotaxin stimulate cell motility of neoplastic and non-neoplastic cells through LPA1

• DOI: 10.1074/jbc.m313927200
• 发表时间: 2004-04-23
• 期刊: JOURNAL OF BIOLOGICAL CHEMISTRY
• 影响因子: 4.8
• 作者: Hama, K;Aoki, J;Suzuki, R
• 通讯作者: Suzuki, R

Hama K et al.: "Lysophosphatidic Acid and Autotaxin Stimulate Cell Motility of Neoplastic and Non-neoplastic Cells Through LPAL."J.Biol.Chem.. (In press).

Hama K 等人：“溶血磷脂酸和自分泌运动因子通过 LPAL 刺激肿瘤和非肿瘤细胞的细胞运动。”J.Biol.Chem..（正在出版）。