Estrogen abrogates transcervical tight junctional resistance by acceleration of occludin modulation.
Estrogen abrogates transcervical tight junctional resistance by acceleration of occludin modulation.
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DOI：
10.1210/jc.2004-0823
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发表时间：
2004-10
期刊：
影响因子：
--
通讯作者：
R. Zeng;Xin Li;G. Gorodeski
中科院分区：
文献类型：
--
作者：
R. Zeng;Xin Li;G. Gorodeski
本研究探讨了雌激素对经宫颈紧结抵抗（R(TJ)）的影响及其机制。用17 -雌二醇处理培养的人宫颈上皮细胞，R（TJ）呈时间和剂量相关性降低。雌激素对E-Cadherin、occluden-1、Claudin-4的表达无显著影响。相反，17 -雌二醇调节跨膜紧密连接蛋白occludin的表达：低浓度（1和10 nm）雌二醇增加了65-kDa形式的occludin的密度，但在更高浓度（100 nm）雌二醇仅诱导这种形式的密度轻度增加2倍。雌二醇也增加occludin 50-kDa形式的表达，并呈剂量相关。雌二醇的R（TJ）和occludin作用是可逆的，可以被他莫昔芬阻断，而黄体酮不能。目前的结果排除了雌激素调节occludin转录的可能性。相反，研究结果表明，雌激素的occludin效应涉及翻译后occludin转换的上调，包括合成和降解。将雌激素对occludin表达的影响与细胞外添加的蛋白酶- k、纤溶酶和基质金属蛋白酶-2的影响进行比较。这三种蛋白酶不可逆地消除了R(TJ)，并诱导低分子量形式的occludin重新表达。然而，后者与雌激素的作用不同，雌激素只产生单一的50 kda形式。总的来说，目前的数据表明，occludin 50-kDa形式是雌激素特异性诱导的occludin亚型，并且经宫颈R（TJ）的雌激素消除机制涉及occludin调节。
The present study explored the effects of estrogen on transcervical tight-junctional resistance (R(TJ)) and the mechanisms involved. Treatment of cultured human cervical epithelial cells with 17beta-estradiol decreased in a time- and dose-related manner the R(TJ). Estrogen had no significant effect on the expression of E-Cadherin, zonula-occluden-1, or Claudin-4. In contrast, 17beta-estradiol modulated expression of the transmembrane tight-junctional protein occludin: at low concentrations (1 and 10 nm) estradiol increased the density of occludin 65-kDa form but at the higher concentration of 100 nm estradiol induced only a mild 2-fold increase in the density of this form. Estradiol also increased the expression of occludin 50-kDa form in a dose-related manner. The R(TJ) and occludin effects of estradiol were reversible and could be blocked by tamoxifen but not progesterone. The present results rule out estrogen modulation of occludin transcription. In contrast, the results suggest that the occludin effects of estrogen involve posttranslational up-regulation of occludin turnover, including synthesis and degradation. The effects of estrogen on occludin expression were compared with those of proteinase-K, plasmin, and matrix-metaloproteinase-2 (all added extracellularly). The three proteinases abrogated irreversibly the R(TJ) and induced expression de novo of occludin low-molecular-weight forms. The latter, however, differed from the effect of estrogen, which generated only a single 50-kDa form. Collectively, the present data suggest that the occludin 50-kDa form is an estrogen-specific-induced occludin isoform and that the mechanism of estrogen-abrogation of transcervical R(TJ) involves occludin modulation.