Vascular repair after menstruation involves regulation of vascular endothelial growth factor-receptor phosphorylation by sFLT-1
Vascular repair after menstruation involves regulation of vascular endothelial growth factor-receptor phosphorylation by sFLT-1
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DOI：
10.1016/s0002-9440(10)64091-6
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发表时间：
2001-04-01
影响因子：
6
通讯作者：
Iruela-Arispe, ML
中科院分区：
文献类型：
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作者：
Graubert, MD;Ortega, MA;Iruela-Arispe, ML
月经后子宫内膜的再生需要快速且高度组织化的血管反应，该过程的潜在调节剂包括血管内皮生长因子（VEGF）蛋白家族的成员及其受体。尽管已在子宫内膜中检测到 VEGF 表达，但对子宫内膜周期中 VEGF 产生、受体激活和内皮细胞增殖之间的关系知之甚少。为了更好地确定 VEGF 家族成员在经后修复过程中的相关性，我们评估了整个月经周期中人子宫内膜中配体、受体和受体磷酸化的活性。我们发现 VEGF 在月经开始时显着增加，这是缺氧、转化生长因子-α 和白细胞介素 1 β 叠加效应的结果。 VEGF 受体 FLT-1 和 KDR 遵循相似的模式。然而，通过磷酸化研究确定的 KDR 功能活性表明，KDR 在月经后期和增殖早期被激活。 KDR 磷酸化程度与 sFLT-1 的存在呈负相关。子宫内膜内皮细胞增殖分析显示，在月经后期和增殖早期出现峰值，与 VEGF、VEGF 受体磷酸化和 sFLT-1 的减少相一致。总之，这些结果表明 VEGF 受体激活和随后在月经后期对 sFLT-1 的调节可能有助于人类子宫内膜血管生成和内皮修复的发生。
Regeneration of the endometrium after menstruation requires a rapid and highly organized vascular response, Potential regulators of this process include members of the vascular endothelial growth factor (VEGF) family of proteins and their receptors. Although VEGF expression has been detected in the endometrium, the relationship between VEGF production, receptor activation, and endothelial cell proliferation during the endometrial cycle is poorly understood To better ascertain the relevance of VEGF family members during postmenstrual repair, we have evaluated ligands, receptors, and activity by receptor phosphorylation in human endometrium throughout the menstrual cycle. We found that VEGF is significantly increased at the onset of menstruation, a result of the additive effects of hypoxia, transforming growth factor-alpha, and interleukin-1 beta. Both VEGF receptors, FLT-1 and KDR, followed a similar pattern, However, functional activity of KDR, as determined by phosphorylation studies, revealed activation in the late menstrual and early proliferative phases. The degree of KDR phosphorylation was inversely correlated with the presence of sFLT-1. Endothelial cell proliferation analysis in endometrium showed a peak during the late menstrual and early proliferative phases in concert with the presence of VEGF, VEGF receptor phosphorylation, and decrease of sFLT-1. Together, these results suggest that VEGF receptor activation and the subsequent modulation of sFLT-1 in the late menstrual phase likely contributes to the onset of angiogenesis and endothelial repair in the human endometrium.