Paracellular route is the major urate transport pathway across the blood-placental barrier.
Paracellular route is the major urate transport pathway across the blood-placental barrier.
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DOI：
10.14814/phy2.12013
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发表时间：
2014-05-01
影响因子：
2.5
通讯作者：
Sakurai H
中科院分区：
文献类型：
--
作者：
Uehara I;Kimura T;Tanigaki S;Fukutomi T;Sakai K;Shinohara Y;Ichida K;Iwashita M;Sakurai H
尿酸盐是嘌呤代谢的最终氧化产物，在人体内排泄到尿液中。临床上，血清尿酸盐水平升高是妊娠高血压综合征（PIH）的指征。然而，尿酸盐在胎盘中是如何处理的，在很大程度上仍然是未知的。在这项研究中，我们比较了母体血清尿酸盐水平与脐带血的水平，并研究了BeWo细胞（一种滋养层细胞系）中的尿酸盐转运机制。在获得知情同意后，从在杏林大学医院接受剖宫产术的患者中采集母体和脐带血样本和胎盘。母体血和脐带血之间以及脐带静脉血和动脉血之间的血清尿酸盐水平无显著差异，表明尿酸盐在胎盘处可自由移动，胎儿不是尿酸盐产生的主要来源。RT-PCR和免疫组化结果显示，胎盘合体滋养层细胞和BeWo细胞均表达尿酸盐转运蛋白OAT 4、OAT 10、GLUT 9/URATv 1和ABCG 2。尽管表达上述尿酸盐转运蛋白，但BeWo细胞不摄取尿酸盐。在确认在transwell上培养的这些细胞形成紧密连接后，测量上室和下室之间的尿酸盐转运。尿酸盐以非饱和动力学通过BeWo细胞单层移动，即使在4°C下孵育细胞时也观察到这种移动，表明尿酸盐通过简单扩散通过细胞旁途径移动。母亲和胎儿之间的血清尿酸盐浓度相同，表明尿酸盐可以通过血液-胎盘屏障。使用滋养层来源的BeWo细胞单层，本研究证明尿酸盐通过细胞旁途径穿过BeWo细胞单层。
Urate, the final oxidation product of purine metabolism, is excreted into urine in humans. Clinically, increased serum urate levels are indicative of pregnancy‐induced hypertension (PIH). However, how urate is handled in the placenta is still largely unknown. In this study, we compared maternal serum urate levels with those of umbilical cord blood and investigated urate transport mechanisms in BeWo cells, a trophoblast‐derived cell line. The maternal and umbilical cord blood samples and placentas were collected from patients undergoing cesarean section at Kyorin University Hospital after obtaining informed consents. There were no significant differences in serum urate levels between maternal blood and umbilical cord blood, and between umbilical cord vein and arterial blood, suggesting that urate is freely movable at the placenta and that fetus is not a major source of urate production. RT‐PCR and immunohistochemistry showed that urate transporters including OAT4, OAT10, GLUT9/URATv1 and ABCG2 were expressed in the syncytiotrophoblast cells in the placenta as well as BeWo cells. Despite expressing aforementioned urate transporters BeWo cells did not take up urate. After confirming the formation of tight junctions of these cells cultured on the transwell, urate transport between upper and lower chambers was measured. Urate moved through BeWo cell monolayers with nonsaturation kinetics and this movement was observed even when the cells were incubated at 4°C, suggesting that urate moves through the paracellular route by simple diffusion. Serum urate concentration was identical between mother and fetus, indicating that urate can pass through blood‐placental barrier. Using trophoblast‐derived BeWo cell monolayer, this study demonstrated that urate moved through BeWo cell monolayer via paracellular route.