Estrogen Stimulates Homing of Endothelial Progenitor Cells to Endometriotic Lesions.
Estrogen Stimulates Homing of Endothelial Progenitor Cells to Endometriotic Lesions.
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DOI：
10.1016/j.ajpath.2016.04.004
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发表时间：
2016-08
期刊：
影响因子：
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通讯作者：
Jeannette Rudzitis-Auth;A. Nenicu;R. Nickels;M. Menger;M. Laschke
中科院分区：
文献类型：
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作者：
Jeannette Rudzitis-Auth;A. Nenicu;R. Nickels;M. Menger;M. Laschke
内皮祖细胞(EPC)进入微血管有助于子宫内膜异位病变的血管化。在此，我们分析了这一血管生成过程是否受雌激素的调节。对雌激素和赋形剂处理的人内皮祖细胞的迁移和管道形成进行了分析。用FVB/N-TGN(Tie2/Green Follow Protein)287 Sato小鼠的骨髓重建辐射后的FVB/N小鼠子宫内膜异位症。给动物灌胃100μg/kgβ-17-戊酸雌二醇酯或赋形剂(对照组)，连续7天和28天。通过高分辨率超声、卡尺测量、组织学和免疫组织化学方法分析病变生长、囊性形成、绿色荧光蛋白+/Tie2+内皮祖细胞归巢、血管生成、细胞增殖和细胞凋亡。用流式细胞术检测血液循环中内皮祖细胞的数量。在体外，雌激素处理的内皮祖细胞显示出比对照组更高的迁移和成管能力，在体内，循环内皮祖细胞的数量不受雌激素的影响。然而，雌激素显著增加了病变微血管中内皮祖细胞的数量，导致早期血管形成的改善。雌激素进一步刺激了病变的生长，病变表现为腺体大量扩张，间质层变平。这主要是由于腺体分泌活性增加，而细胞增殖和凋亡没有受到明显影响。这些发现表明，子宫内膜异位症病变中的血管生成依赖于雌激素，这为子宫内膜异位症复杂的病理生理增加了一种新的激素调节机制。
The incorporation of endothelial progenitor cells (EPCs) into microvessels contributes to the vascularization of endometriotic lesions. Herein, we analyzed whether this vasculogenic process is regulated by estrogen. Estrogen- and vehicle-treated human EPCs were analyzed for migration and tube formation. Endometriotic lesions were induced in irradiated FVB/N mice, which were reconstituted with bone marrow from FVB/N-TgN (Tie2/green fluorescent protein) 287 Sato mice. The animals were treated with 100 μg/kg β-estradiol 17-valerate or vehicle (control) over 7 and 28 days. Lesion growth, cyst formation, homing of green fluorescent protein+/Tie2+EPCs, vascularization, cell proliferation, and apoptosis were analyzed by high-resolution ultrasonography, caliper measurements, histology, and immunohistochemistry. Numbers of blood circulating EPCs were assessed by flow cytometry.In vitro, estrogen-treated EPCs exhibited a higher migratory and tube-forming capacity when compared with controls.In vivo, numbers of circulating EPCs were not affected by estrogen. However, estrogen significantly increased the number of EPCs incorporated into the lesions' microvasculature, resulting in an improved early vascularization. Estrogen further stimulated the growth of lesions, which exhibited massively dilated glands with a flattened layer of stroma. This was mainly because of an increased glandular secretory activity, whereas cell proliferation and apoptosis were not markedly affected. These findings indicate that vasculogenesis in endometriotic lesions is dependent on estrogen, which adds a novel hormonally regulated mechanism to the complex pathophysiology of endometriosis.