Protective role of GPR120 in themaintenance of pregnancy by promoting decidualization via regulation of glucose metabolism
Protective role of GPR120 in themaintenance of pregnancy by promoting decidualization via regulation of glucose metabolism
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GPR120 通过调节葡萄糖代谢促进蜕膜化对维持妊娠的保护作用
DOI：
10.1016/j.ebiom.2018.12.019
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发表时间：
2019-01-01
期刊：
影响因子：
11.1
通讯作者：
Zhang, Yanyun
中科院分区：
文献类型：
--
作者：
Huang, Jiefang;Xue, Mingxing;Zhang, Yanyun
背景资料：摄入omega-3 PUFA已被证明对妊娠结局有积极影响，其受体GPR 120调节多种细胞功能，包括分化，代谢和免疫反应。方法：收集正常妊娠和自然流产妇女的蜕膜组织，检测GPR 120的表达谱。建立小鼠流产模型和人工诱导蜕膜瘤模型，观察GPR 120对妊娠结局和体内蜕膜化的影响。采用HESCs和原代DSCs探讨GPR 120在蜕膜化过程中的作用及其机制。结果：我们发现GPR 120通过上调人子宫内膜基质细胞葡萄糖摄取和磷酸戊糖途径（PPP）来促进蜕膜化。第一，GPR 120在自然流产蜕膜中的表达较正常蜕膜下调。缺乏GPR 120使小鼠易受LPS或RU 486诱导的流产。通过改善GLUT 1介导的葡萄糖摄取和G6 PD介导的PPP，GPR 120增强了蜕膜化。GPR 120通过激活ERK 1/2和AMPK信号转导上调FOXO 1，并增加GLUT 1的表达。此外，GPR 120可增强蜕膜基质细胞中趋化因子和细胞因子的表达。结论：GPR 120在小鼠蜕膜化和妊娠维持中起重要作用，可能成为自然流产诊断和治疗的潜在靶点。基金：国家科学技术部、国家自然科学基金、上海市科委项目。(c)2018作者由爱思唯尔公司出版
Background: Intake of omega-3 PUFAs have been demonstrated to have positive effects on pregnancy outcome, whose receptor, GPR120, regulates several cellular functions including differentiation, metabolism and immune reaction. However, whether GPR120 is involved in decidualization and pregnancy remains unknown.Methods: Decidua tissue from women with normal pregnancy and spontaneous abortion were collected to determine the expression profile of GPR120. Abortion mouse models and artificially induced deciduoma in mice were established to evaluate the effect of GPR120 on pregnancy outcome and in vivo decidualization. HESCs and primary DSCs were used to explore the roles of GPR120 in decidualization and mechanisms involved.Findings: We found that GPR120 functioned to promote decidualization by upregulating glucose uptake and pentose-phosphate pathway (PPP) of human endometrial stromal cells. Firstly, the expression of GPR120 in decidua of spontaneous abortion was downregulated compared to normal decidua. Lack of GPR120 predisposed mice to LPS or RU486 induced abortion. Decidualization was augmented by GPR120 via improving GLUT1-mediated glucose uptake and G6PD-mediated PPP. FOXO1 was upregulated by GPR120 via activation of ERK1/2 and AMPK signaling and increased the expression of GLUT1. Furthermore, the expression of chemokines and cytokines in decidual stromal cells was enhanced by GPR120. Lastly, GPR120 agonist ameliorated LPS-induced abortion in the mice.Interpretation: GPR120 plays significant roles in decidualization and the maintenance of pregnancy, which might be a potential target for diagnosis and treatment of spontaneous abortion.Fund: Ministry of Science and Technology of China, National Natural Science Foundation of China, the Program of Science and Technology Commission of Shanghai Municipality. (c) 2018 The Authors. Published by Elsevier B.V.