Estrogen decreases the expression of claudin-5 in vascular endothelial cells in the murine uterus
Estrogen decreases the expression of claudin-5 in vascular endothelial cells in the murine uterus
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DOI：
10.1507/endocrj.ej13-0442
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发表时间：
2014-07-01
影响因子：
2
通讯作者：
Terada, Nobuyuki
中科院分区：
文献类型：
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作者：
Hata, Masaki;Yamanegi, Koji;Terada, Nobuyuki
血管内皮（VE）-钙粘蛋白和claudin-5分别是血管内皮细胞的粘附和紧密连接的主要成分，其表达的减少与内皮细胞旁通透性的增加有关。在子宫内，雌激素引起子宫内膜水肿。然而，雌激素对内皮细胞旁通透性的体内作用尚不清楚。因此，我们研究了雌激素或孕激素刺激小鼠子宫血管内皮细胞中VE-钙粘蛋白和claudin-5的表达。以24小时的间隔向切除卵巢的成熟小鼠注射雌二醇-17 β（1 μ g/小鼠）或孕酮（1 mg/小鼠），持续6天。使用双重免疫荧光法对这些小鼠和未处理小鼠的子宫的冷冻横切面进行CD 31（血管内皮细胞标记物）加VE-钙粘蛋白或密蛋白-5染色。然后，检查子宫内膜中CD 31阳性血管中VE-钙粘蛋白或密蛋白-5阳性血管的百分比。VE-钙粘蛋白和claudin-5在未治疗小鼠的延髓中的大多数CD 31阳性血管中表达。预后不影响VE-cadherin和claudin-5的表达，雌二醇-17 β也不影响VE-cadherin的表达，但雌二醇-17 β显著降低claudin-5的表达。从24小时后检测到雌二醇1 -17 β的这种降低作用，此时每个子宫的含水量显著增加。目前的研究表明，雌激素，而不是孕激素，降低了小鼠子宫内膜血管内皮细胞中的claudin-5的表达，从24小时后，这表明claudin-5表达的减少有助于雌激素刺激后的子宫内膜水肿后期。
Vascular endothelial (VE)-cadherin and claudin-5 are major components of the adherens and tight junctions of vascular endothelial cells, respectively, and decreases in their expression are associated with increases in endothelial paracellular permeability. In the uterus, estrogen induces endometrial edema. However, the in vivo effect of estrogen on endothelial paracellular permeability is unknown. Therefore, we studied the expression of VE-cadherin and claudin-5 in vascular endothelial cells in murine uteri stimulated by estrogen or progesterone. Ovariectomized mature mice were injected with estradiol-17 beta (1 mu g/mouse) or progesterone (1 mg/mouse) at intervals of 24 hours for 6 days. The frozen transverse sections of the uteri of these mice and untreated mice were stained for CD31 (vascular endothelial cell marker) plus VE-cadherin or claudin-5 using a double-immunofluorescence method. Then, the percentages of VE-cadherin- or claudin-5-positive vessels among CD31-positive vessels were examined in the uterine endometria. VE-cadherin and claudin-5 were expressed in most CD31-positive vessels in the endometria of the untreated mice. Progesterone did not affect the expression of both VE-cadherin and claudin-5 and estradio1-17 beta also did not affect the VE-cadherin expression, but estradio1-17 beta significantly decreased the claudin-5 expression. This decreasing effect of estradio1-17 beta was detected from 24 hours later when the water content per a uterus significantly increased. The present study indicates that estrogen, but not progesterone, decreases the expression of claudin-5 in vascular endothelial cells in the murine uterine endometrium from 24 hours later, suggesting that the decrease in the claudin-5 expression contributes to the endometrial edema late after the estrogen stimulation.