The Role of 17β-Estrogen in Candida albicans Adhesion on Human Vaginal Epithelial Cells via FAK Phosphorylation

The Role of 17β-Estrogen in Candida albicans Adhesion on Human Vaginal Epithelial Cells via FAK Phosphorylation
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17β-雌激素通过 FAK 磷酸化在白色念珠菌粘附人阴道上皮细胞中的作用

DOI:
10.1007/s11046-020-00440-1
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发表时间:
2020-03-17
期刊:
影响因子:
5.5
通讯作者:
Zeng, Xin
Zeng, Xin
中科院分区:
生物学3区
文献类型:
--
作者:
Luan, Ting;Liu, Xia;Zeng, Xin

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目的探讨17 β-雌激素在白念珠菌中的作用。白色念珠菌)粘附在外阴阴道念珠菌病(VVC)中的人阴道上皮细胞上。方法采用阴道上皮细胞株VK 2/E6 E7,研究雌激素诱导的C.白色念珠菌和细胞。进行粘附研究以评估雌激素依赖性粘着斑激酶(FAK)活化在细胞粘附中的参与。通过蛋白质印迹法评估雌激素激发后FAK和雌激素受体α(ER α)的磷酸化状态。ER α的特异性抑制剂用于验证ER α-FAK信号级联的参与。结果1000 nM雌激素刺激48 h后,ER α和FAK出现短暂激活,C.白色念珠菌粘附在每个阴道上皮细胞上。雌激素诱导的ER α和FAK的激活被ER α的特异性抑制剂抑制,特别是当抑制剂达到10 μ M浓度并允许作用12小时时。同时,粘附的C.观察到白色念珠菌。然而,随着雌激素浓度的增加,这种抑制作用减弱。结论FAK和ER α信号通路参与了阴道上皮细胞与C.白念珠菌VVC的形成与细胞粘附增强有关,一定浓度的雌激素可促进VVC的形成。
Purposes To investigate the role of 17 beta-estrogen in Candida albicans (C. albicans) adhesion on human vaginal epithelial cells in vulvovaginal candidiasis (VVC). Methods The vaginal epithelial cell line, VK2/E6E7, was used to study the estrogen-induced molecular events between C. albicans and cells. An adhesion study was performed to evaluate the involvement of the estrogen-dependent focal adhesion kinase (FAK) activation in cell adhesion. The phosphorylation status of FAK and estrogen receptor alpha (ER alpha) upon estrogen challenge was assessed by western blotting. Specific inhibitors for ER alpha were used to validate the involvement of ER alpha-FAK signaling cascade. Results A transient activation of ER alpha and FAK was observed following the stimulation with 1000 nM estrogen for 48 h, as well as the increased average number of C. albicans adhering to each vaginal epithelial cell. Estrogen-induced activation of ERa and FAK was inhibited by the specific inhibitor of ER alpha, especially when the inhibitor reached a 10 mu M concentration and allowed to act for 12 h. Simultaneously, a decrease in the number of adherent C. albicans was observed. However, this inhibitory effect diminished as the concentration of estrogen increased. Conclusion FAK and ER alpha signaling cascades were involved in the early interaction between the vaginal epithelial cells and C. albicans, which appeared to be linked with the enhanced cell adhesion leading to VVC and promoted by a certain concentration of estrogen.