Prostaglandin E2 regulation of amnion cell vascular endothelial growth factor expression: relationship with intramembranous absorption rate in fetal sheep.
Prostaglandin E2 regulation of amnion cell vascular endothelial growth factor expression: relationship with intramembranous absorption rate in fetal sheep.
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DOI：
10.1152/ajpregu.00070.2014
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发表时间：
2014-08
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通讯作者：
C. Cheung;Michael K Beardall;Debra F. Anderson;R. Brace
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作者：
C. Cheung;Michael K Beardall;Debra F. Anderson;R. Brace
我们假设，前列腺素E2（PGE 2）刺激羊水运输通过羊膜血管内皮生长因子（VEGF）在羊膜细胞中的表达上调和羊水中的PGE 2浓度呈正相关，与膜内（IM）吸收率在胎羊。在培养的绵羊羊膜细胞中分析了一定浓度范围的PGE 2对VEGF 164和小窝蛋白-1基因表达的影响。在对照条件、等容胎尿置换（低IM吸收率）或羊水内输注（高IM吸收率）期间，测定妊娠晚期胎羊的IM吸收率、羊水（AF）体积和AF中的PGE 2浓度。在绵羊羊膜细胞中，PGE 2诱导VEGF 164 mRNA水平的剂量和时间依赖性增加，并降低小窝蛋白-1 mRNA和蛋白水平。VEGF受体阻断剂消除了小窝蛋白-1的反应，而最低限度地影响VEGF对PGE 2的反应。在绵羊胎儿中，尿液替代使羊水中PGE 2浓度降低了58%，IM吸收率降低了一半，AF体积增加了一倍（P < 0.01）。羊水内灌注可增加IM吸收率和AF体积（P < 0.01），而羊水中PGE 2浓度无明显变化。在每个实验条件下，IM吸收率和AF体积均与羊水PGE 2浓度无关。尽管微摩尔浓度的PGE 2诱导培养的羊膜细胞中VEGF和小窝蛋白-1基因表达的剂量依赖性反应与PGE 2在激活VEGF以介导AF跨羊膜转运中的作用一致，但生理纳摩尔浓度的羊膜PGE 2似乎不调节IM吸收速率或AF体积。
We hypothesized that prostaglandin E2 (PGE2) stimulates amniotic fluid transport across the amnion by upregulating vascular endothelial growth factor (VEGF) expression in amnion cells and that amniotic PGE2 concentration correlates positively with intramembranous (IM) absorption rate in fetal sheep. The effects of PGE2 at a range of concentrations on VEGF 164 and caveolin-1 gene expressions were analyzed in cultured ovine amnion cells. IM absorption rate, amniotic fluid (AF) volume, and PGE2 concentration in AF were determined in late-gestation fetal sheep during control conditions, isovolumic fetal urine replacement (low IM absorption rate), or intra-amniotic fluid infusion (high IM absorption rate). In ovine amnion cells, PGE2 induced dose- and time-dependent increases in VEGF 164 mRNA levels and reduced caveolin-1 mRNA and protein levels. VEGF receptor blockade abolished the caveolin-1 response, while minimally affecting the VEGF response to PGE2. In sheep fetuses, urine replacement reduced amniotic PGE2 concentration by 58%, decreased IM absorption rate by half, and doubled AF volume (P < 0.01). Intra-amniotic fluid infusion increased IM absorption rate and AF volume (P < 0.01), while amniotic PGE2 concentration was unchanged. Neither IM absorption rate nor AF volume correlated with amniotic PGE2 concentration under each experimental condition. Although PGE2 at micromolar concentrations induced dose-dependent responses in VEGF and caveolin-1 gene expression in cultured amnion cells consistent with a role of PGE2 in activating VEGF to mediate AF transport across the amnion, amniotic PGE2 at physiological nanomolar concentrations does not appear to regulate IM absorption rate or AF volume.