小电导钙激活钾通道 3（SK3）是子宫内膜生长过程中子宫内膜重塑的调节剂。
Small-conductance, calcium-activated potassium channel 3 (SK3) is a modulator of endometrial remodeling during endometrial growth.
机构信息
The Key Laboratory of Reproductive Genetics (Y.-C.L., J.Y., G.-L.D., S.S., D.Z., L.J., J.-X.P., X.-H.L., Y.-M.Z., J.-Z.S., H.-F.H.), Ministry of Education (Zhejiang University), Department of Reproductive Endocrinology (Y.-C.L., J.Y., G.-L.D., D.Z., L.J., J.-X.P., X.-H.L., Y.-M.Z., H.-F.H.), Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310006, China; Department of Pathology and Pathophysiology (S.S., J.-Z.S.), School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310058, China; and International Peace Maternity and Child Health Hospital (H.-F.H.), Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China.
出版信息
J Clin Endocrinol Metab. 2014 Oct;99(10):3800-10. doi: 10.1210/jc.2013-3389. Epub 2014 Jun 30.
BACKGROUND
Small-conductance, Ca(2+)-activated K(+) channel 3 (SK3) has been shown to be expressed in porcine endometrium. However, the roles of SK3 in human endometrium during the menstrual cycle and early pregnancy are unknown.
OBJECTIVE
The objective of the study was to investigate the expression and function of SK3 in human endometrium and the mechanism involved.
METHODS
We determined the expression of SK3 in human endometrium by RT-PCR, Western blotting, and immunofluorescence. Using electrophysiological and fluorescent imaging techniques, we investigated the effects of SK3 on the membrane potential and the concentrations of cytosolic calcium, respectively. The effects of SK3 on endometrial thickness and pregnancy outcome were also investigated. Knockdown of endometrial SK3 was used to examine the effects of SK3 on cell migration, cytoskeleton formation, and calcium concentration in the cytosol.
RESULTS
SK3 channels are present in human endometrium. In vivo experimental and clinical data demonstrated that the reduced expression of SK3 was associated with a thin endometrium and unsuccessful pregnancy outcomes. Knockdown of human endometrial SK3 attenuated the rise in cytosolic calcium and membrane hyperpolarization induced by thapsigargin, a Ca(2+)-ATPase inhibitor, cell migration, and F-actin assembly. Knockdown of endometrial SK3 in mice also resulted in a thin endometrium and unsuccessful pregnancy outcome.
CONCLUSIONS
These observations demonstrate that SK3 channels are expressed in human endometrial cells. Reduced SK3 expression attenuates endometrial cell migration and is associated with unsuccessful pregnancy outcomes.
背景
小电导钙激活钾通道 3（SK3）已被证明在猪子宫内膜中表达。然而，SK3 在人类子宫内膜在月经周期和早孕期间的作用尚不清楚。
目的
本研究旨在探讨 SK3 在人子宫内膜中的表达和功能及其相关机制。
方法
我们通过 RT-PCR、Western blot 和免疫荧光法确定 SK3 在人子宫内膜中的表达。我们使用电生理和荧光成像技术分别研究了 SK3 对膜电位和细胞浆钙离子浓度的影响。还研究了 SK3 对子宫内膜厚度和妊娠结局的影响。通过敲低子宫内膜 SK3，研究了 SK3 对细胞迁移、细胞骨架形成和细胞浆钙离子浓度的影响。
结果
SK3 通道存在于人子宫内膜中。体内实验和临床数据表明，SK3 的表达减少与子宫内膜薄和妊娠结局不良有关。敲低人子宫内膜 SK3 可减弱钙调素抑制剂 thapsigargin 诱导的细胞浆钙离子升高和膜超极化、细胞迁移和 F-肌动蛋白组装。敲低小鼠子宫内膜 SK3 也导致子宫内膜变薄和妊娠结局不良。
结论
这些观察结果表明，SK3 通道在人子宫内膜细胞中表达。SK3 表达减少会减弱子宫内膜细胞的迁移能力，并与妊娠结局不良有关。
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