早期妊娠過程中，滋養(yǎng)層細(xì)胞對母體組織的正常侵潤涉及復(fù)雜的分子對話和調(diào)控,，是決定正常胎盤形成以及正常妊娠的一個關(guān)鍵因素,。滋養(yǎng)層細(xì)胞的侵潤機(jī)制與腫瘤細(xì)胞的轉(zhuǎn)移有諸多相似性，但與腫瘤細(xì)胞截然不同的是,，滋養(yǎng)層細(xì)胞對于子宮的侵潤受到來自母體和自身的多種旁分泌/自分泌因子的嚴(yán)格調(diào)控,。
CXCL14是一種與免疫細(xì)胞趨化、腫瘤遷移密切相關(guān)的趨化因子,。近日,，中科院動物研究所段恩奎研究員帶領(lǐng)的研究小組通過基因芯片篩選以及多種實驗手段證明，在小鼠和人類妊娠中,，CXCL14在早期母胎界面呈現(xiàn)高表達(dá),，并特異地定位于滋養(yǎng)層細(xì)胞。進(jìn)一步的功能研究發(fā)現(xiàn)CXCL14能夠有效地抑制滋養(yǎng)層細(xì)胞的侵潤,，這一作用是通過調(diào)節(jié)滋養(yǎng)層MMP-9和MMP-2的分泌量和活性來實現(xiàn)的,。另外，因為CXCL14的特異性受體目前尚未發(fā)現(xiàn),，文章作者通過用生物素標(biāo)記的CXCL14在母胎界面進(jìn)行特異結(jié)合實驗,，發(fā)現(xiàn)CXCL14特異地結(jié)合于滋養(yǎng)層細(xì)胞，而不結(jié)合于蛻膜細(xì)胞，這提示滋養(yǎng)層細(xì)胞是CXCL14在母胎界面的靶細(xì)胞,，并表達(dá)CXCL14的受體,。以上結(jié)果揭示了CXCL14是早期妊娠中母胎界面負(fù)調(diào)控滋養(yǎng)層侵潤的一個重要因子。
相關(guān)研究結(jié)果分別發(fā)表于Journal of cellular physiology(2009 Nov;221(2):448-57.) 和Endocrinology (2009 Oct 15. Epub ahead of print),。 這項工作得到了中科院動物研究所知識創(chuàng)新工程項目和“973"項目的資助,。（生物谷Bioon.com）
生物谷推薦原始出處：
Journal of Cellular Physiology 22 Jul 2009
CXCL14 inhibits trophoblast outgrowth via a paracrine/autocrine manner during early pregnancy in mice
Haibin Kuang 1 2 3, Qi Chen 1 2, Xiujun Fan 1 2, Ying Zhang 1 2, Li Zhang 1 2, Hongying Peng 1, Yujing Cao 1, Enkui Duan 1 *
1State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, P.R. China
2Graduate School of the Chinese Academy of Sciences, Beijing, P.R. China
3Department of Physiology, School of Medicine, Nanchang University, Nanchang, P.R. China
CXCL14, a member of chemokine family, was previously known to participate in many pathophysiological events, such as leukocytes recruitment and tumor suppression. However, it remained largely unknown whether CXCL14 is a physiological player during early pregnancy. In this regard, our recent global gene microarray analysis has observed an implantation-specific expression profile of CXCL14 mRNA during early pregnancy in mice, showing its higher levels at implantation sites compared to inter-implantation sites, implicating a potential role of CXCL14 in the periimplantation events. In the present investigation, using Northern blot, in situ hybridization and immunostaining, we further demonstrated that uterine CXCL14 expression was specifically induced at embryo implantation site and expanded with subsequent decidualization process in a spatiotemporal manner. The implanting embryo also showed a highlighted expression of CXCL14 in the blastocyst trophectoderm and its derived ectoplacental cones (EPCs) during postimplantation development. In vitro functional study revealed that CXCL14 could significantly inhibit both primary and secondary trophoblast attachment and outgrowth, correlated with a stage-dependant downregulation of MMP-2 and/or MMP-9 activity. Moreover, it was found that biotinylated CXCL14 could specifically bind to trophoblast cells in vitro and in vivo, suggesting trophoblast cell, perhaps expressing the unidentified CXCL14 receptor, is a bioactive target of CXCL14. Collectively, our findings provide evidences supporting the contention that CXCL14 is an important paracrine/autocrine modulator regulating trophoblast outgrowth at the maternal-fetal interface during the process of pregnancy establishment. This study is clinically related since CXCL14 is also highly expressed in human receptive endometrium and trophoblasts.
