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胚胎-上皮边界处的自分泌运动因子-溶血磷脂酸-LPA信号传导控制着蜕膜化途径。

Autotaxin-lysophosphatidic acid-LPA signaling at the embryo-epithelial boundary controls decidualization pathways.

作者信息

Aikawa Shizu, Kano Kuniyuki, Inoue Asuka, Wang Jiao, Saigusa Daisuke, Nagamatsu Takeshi, Hirota Yasushi, Fujii Tomoyuki, Tsuchiya Soken, Taketomi Yoshitaka, Sugimoto Yukihiko, Murakami Makoto, Arita Makoto, Kurano Makoto, Ikeda Hitoshi, Yatomi Yutaka, Chun Jerold, Aoki Junken

机构信息

Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Miyagi, Japan.

Japan Agency for Medical Research and Development, Core Research for Evolutional Science and Technology (AMED-CREST), Chiyoda-ku, Tokyo, Japan.

出版信息

EMBO J. 2017 Jul 14;36(14):2146-2160. doi: 10.15252/embj.201696290. Epub 2017 Jun 6.

DOI:10.15252/embj.201696290
PMID:28588064
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5509998/
Abstract

During pregnancy, up-regulation of heparin-binding (HB-) EGF and cyclooxygenase-2 (COX-2) in the uterine epithelium contributes to decidualization, a series of uterine morphological changes required for placental formation and fetal development. Here, we report a key role for the lipid mediator lysophosphatidic acid (LPA) in decidualization, acting through its G-protein-coupled receptor LPA in the uterine epithelium. Knockout of or inhibition of the LPA-producing enzyme autotaxin (ATX) in pregnant mice leads to HB-EGF and COX-2 down-regulation near embryos and attenuates decidual reactions. Conversely, selective pharmacological activation of LPA induces decidualization via up-regulation of HB-EGF and COX-2. ATX and its substrate lysophosphatidylcholine can be detected in the uterine epithelium and in pre-implantation-stage embryos, respectively. Our results indicate that ATX-LPA-LPA signaling at the embryo-epithelial boundary induces decidualization via the canonical HB-EGF and COX-2 pathways.

摘要

在怀孕期间，子宫上皮中肝素结合（HB-）表皮生长因子和环氧化酶-2（COX-2）的上调有助于蜕膜化，这是胎盘形成和胎儿发育所需的一系列子宫形态变化。在此，我们报告脂质介质溶血磷脂酸（LPA）在蜕膜化过程中起关键作用，它通过其在子宫上皮中的G蛋白偶联受体LPA发挥作用。敲除或抑制怀孕小鼠中产生LPA的酶自分泌运动因子（ATX）会导致胚胎附近的HB-EGF和COX-2下调，并减弱蜕膜反应。相反，LPA的选择性药理激活通过上调HB-EGF和COX-2诱导蜕膜化。分别可以在子宫上皮和植入前阶段的胚胎中检测到ATX及其底物溶血磷脂酰胆碱。我们的结果表明，胚胎-上皮边界处的ATX-LPA-LPA信号通过经典的HB-EGF和COX-2途径诱导蜕膜化。

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