期刊
EMBO JOURNAL
卷 36, 期 14, 页码 2146-2160出版社
WILEY
DOI: 10.15252/embj.201696290
关键词
autotaxin; decidualization; embryo implantation; LPA(3); lysophosphatidic acid
资金
- AMED-CREST (Japan Agency for Medical Research and Development, Core Research for Evolutional Science and Technology)
- PRESTO (Japan Science and Technology Agency, Precursory Research for Embryonic Science and Technology)
- Ministry of Education, Culture, Sports, Science and Technology (MEXT)
- Grants-in-Aid for Scientific Research [26670030, 17H03990, 16H05469, 15H04648, 15H05898, 16K15701, 16K15700, 15H05897, 15H04979, 16H04679, 15H05905, 17K08233, 16K15122] Funding Source: KAKEN
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(3) in the uterine epithelium. Knockout of Lpar(3) 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(3) 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(3) signaling at the embryoepithelial boundary induces decidualization via the canonical HB-EGF and COX-2 pathways.
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