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新型大麻素受体 - GPR55 在大鼠胎仔胎盘发育过程中的调控作用。

Modulation of the novel cannabinoid receptor - GPR55 - during rat fetoplacental development.

机构信息

Laboratório de Bioquímica, Departamento Ciências Biológicas, Faculdade de Farmácia da Universidade do Porto, R. Aníbal Cunha n° 164, 4050-047 Porto, Portugal.

出版信息

Placenta. 2011 Jun;32(6):462-9. doi: 10.1016/j.placenta.2011.03.007. Epub 2011 Apr 16.

DOI:10.1016/j.placenta.2011.03.007
PMID:21497900
Abstract

Decidualization process involves the morphological and functional transformation of endometrial stromal cells into decidual cells. This is a finely regulated process, which involves proliferation and differentiation of stromal cells into decidual cells, which is followed by regression of the decidual tissue, mainly by apoptosis, necessary to accommodate the growing embryo. Together with the endogenous cannabinoids (ECs) and the respective metabolizing-enzymes, the cannabinoid receptors complete the endocannabinoid system (ECS). Two cannabinoid receptors have been described so far, CB1 and CB2, though a third has been suggested, CB3. Although the ECS role in several biological functions, including reproductive processes, is now well documented, the current state of knowledge about this system is still incomplete. In order to investigate the expression of GPR55, referred as the novel cannabinoid receptor 3 (CB3), in the uterine maternal tissues during normal pregnancy we analysed its expression by Q-PCR, Western blot and immunohistochemistry during fetoplacental period. We found higher protein levels on day 14, after full development of mesometrial decidua. In addition, GPR55 was found in uterine natural killer (uNK) cells pointing to an involvement in the immunological reactions that occur during pregnancy. The prominent expression of GPR55 in decidual cells suggests a role in mediating cannabinoid signalling during fetoplacental development. Additionally, we have studied the effects resulting from its activation in primary decidual cell cultures, which revealed a potential modulation of cell viability through GPR55. The data presented here may clarify the role of GPR55 in fetoplacental development and highlights the presence of a new target for cannabinoid signalling during pregnancy.

摘要

蜕膜化过程涉及子宫内膜基质细胞向蜕膜细胞的形态和功能转化。这是一个精细调控的过程,涉及基质细胞的增殖和分化为蜕膜细胞,随后蜕膜组织退化,主要通过凋亡,以适应不断生长的胚胎。内源性大麻素(ECs)及其各自的代谢酶与大麻素受体一起构成了内源性大麻素系统(ECS)。迄今为止,已经描述了两种大麻素受体,CB1 和 CB2,但有人提出了第三种,即 CB3。尽管 ECS 在包括生殖过程在内的多种生物学功能中的作用现在已经得到很好的证明,但对该系统的当前认识仍然不完整。为了研究在正常妊娠期间子宫母体组织中被称为新型大麻素受体 3(CB3)的 GPR55 的表达,我们通过 Q-PCR、Western blot 和免疫组织化学分析了其在胎盘中的表达在胎盘中。我们发现,在中系膜蜕膜完全发育后的第 14 天,蛋白水平更高。此外,GPR55 存在于子宫自然杀伤(uNK)细胞中,表明其参与了妊娠期间发生的免疫反应。GPR55 在蜕膜细胞中的高表达表明其在介导胎盘中大麻素信号传递中起作用。此外,我们还研究了其在原代蜕膜细胞培养物中激活的结果,结果显示 GPR55 通过 GPR55 潜在地调节细胞活力。这里提出的数据可能阐明 GPR55 在胎盘中的作用,并强调了妊娠期间大麻素信号传递的新靶标。

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