Exposure of decidualized HIESC to low oxygen tension and leucine deprivation results in increased IGFBP-1 phosphorylation and reduced IGF-I bioactivity
Exposure of decidualized HIESC to low oxygen tension and leucine deprivation results in increased IGFBP-1 phosphorylation and reduced IGF-I bioactivity
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DOI：
10.1016/j.mce.2017.04.005
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发表时间：
2017-09-05
影响因子：
4.1
通讯作者：
Gupta, Madhulika B.
中科院分区：
文献类型：
--
作者：
Abu Shehab, Majida;Biggar, Kyle;Gupta, Madhulika B.
蜕膜IGFBP-1的磷酸化增强了IGF-I的结合，限制了这种生长因子的生物利用度，这可能是导致胎盘和胎儿生长减少的原因之一。调节蜕膜IGFBP-1磷酸化的机制还不完全清楚。使用蜕膜化的人类永生化子宫内膜间质细胞，我们测试了低氧分压或亮氨酸可获得性减少，据信在胎盘功能不全中常见，增加蜕膜IGFBP-1的磷酸化的假说。采用多反应监测-质谱仪(MRM-MS)定量检测IGFBP-1的磷酸化水平。MRM-MS证实了IGFBP-1在Ser58位的新的磷酸化，但该位置不受低氧压/亮氨酸剥夺的影响。相反，pSer119、pSer98/pSer101和pSer169/pSer174位点的磷酸化水平显著升高。免疫印迹和使用亚磷酸盐特异性IGFBP-1抗体的双重免疫荧光进一步表明，在这两种处理下，HIESC的IGFBP-1磷酸化水平增加，从而降低了IGF-I的生物活性。这些数据支持一种假设，即在胎盘功能不全时，IGF-I信号的下调与IGFBP-1的过度磷酸化有关，从而限制了胎儿的生长。(C)2017年，爱思唯尔爱尔兰有限公司出版。
Phosphorylation of decidual IGFBP-1 enhances binding of IGF-I, limiting the bioavailability of this growth factor which may contribute to reduced placental and fetal growth. The mechanisms regulating decidual IGFBP-1 phosphorylation are incompletely understood. Using decidualized human immortalized endometrial stromal cells we tested the hypothesis that low oxygen tension or reduced leucine availability, believed to be common in placental insufficiency, increase the phosphorylation of decidual IGFBP-1. Multiple reaction monitoring-MS (MRM-MS) was used to quantify IGFBP-1 phosphorylation. MRM-MS validated the novel phosphorylation of IGFBP-1 at Ser58, however this site was unaffected by low oxygen tension/leucine deprivation. In contrast, significantly elevated phosphorylation was detected for pSer119, pSer98/pSer101 and pSer169/pSer174 sites. Immunoblotting and dual-immunofluorescence using phosphosite-specific IGFBP-1 antibodies further demonstrated increased IGFBP-1 phosphorylation in HIESC under both treatments which concomitantly reduced IGF-I bioactivity. These data support the hypothesis that down regulation of IGF-I signaling links decidual IGFBP-1 hyperphosphorylation to restricted fetal growth in placental insufficiency. (C) 2017 Published by Elsevier Ireland Ltd.