Department of Woman, Child and General and Specialized Surgery, University of Campania "Luigi Vanvitelli", 80138 Naples, Italy.
Department of Obstetrics and Gynecology, "Filippo Del Ponte" Hospital, University of Insubria, 21100 Varese, Italy.
Int J Mol Sci. 2020 Feb 7;21(3):1114. doi: 10.3390/ijms21031114.
Ion channels play a crucial role in many physiological processes. Several subtypes are expressed in the endometrium. Endometriosis is strictly correlated to estrogens and it is evident that expression and functionality of different ion channels are estrogen-dependent, fluctuating between the menstrual phases. However, their relationship with endometriosis is still unclear.
To summarize the available literature data about the role of ion channels in the etiopathogenesis of endometriosis.
A search on PubMed and Medline databases was performed from inception to November 2019.
Cystic fibrosis transmembrane conductance regulator (CFTR), transient receptor potentials (TRPs), aquaporins (AQPs), and chloride channel (ClC)-3 expression and activity were analyzed. CFTR expression changed during the menstrual phases and was enhanced in endometriosis samples; its overexpression promoted endometrial cell proliferation, migration, and invasion throughout nuclear factor kappa-light-chain-enhancer of activated B cells-urokinase plasminogen activator receptor (NFκB-uPAR) signaling pathway. No connection between TRPs and the pathogenesis of endometriosis was found. AQP5 activity was estrogen-increased and, through phosphatidylinositol-3-kinase and protein kinase B (PI3K/AKT), helped in vivo implantation of ectopic endometrium. In vitro, AQP9 participated in extracellular signal-regulated kinases/p38 mitogen-activated protein kinase (ERK/p38 MAPK) pathway and helped migration and invasion stimulating matrix metalloproteinase (MMP)2 and MMP9. ClC-3 was also overexpressed in ectopic endometrium and upregulated MMP9.
Available evidence suggests a pivotal role of CFTR, AQPs, and ClC-3 in endometriosis etiopathogenesis. However, data obtained are not sufficient to establish a direct role of ion channels in the etiology of the disease. Further studies are needed to clarify this relationship.
离子通道在许多生理过程中发挥着关键作用。几种亚型在子宫内膜中表达。子宫内膜异位症与雌激素密切相关，不同离子通道的表达和功能是雌激素依赖性的，在月经周期中波动。然而，它们与子宫内膜异位症的关系尚不清楚。
总结离子通道在子宫内膜异位症发病机制中的作用的现有文献数据。
对 PubMed 和 Medline 数据库进行了从开始到 2019 年 11 月的搜索。
分析了囊性纤维化跨膜电导调节剂（CFTR）、瞬时受体电位（TRP）、水通道蛋白（AQP）和氯离子通道（ClC）-3 的表达和活性。CFTR 的表达在月经周期中发生变化，并在子宫内膜异位症样本中增强；其过表达通过核因子κ轻链增强子的激活 B 细胞-尿激酶纤溶酶原激活受体（NFκB-uPAR）信号通路促进子宫内膜细胞增殖、迁移和侵袭。TRP 与子宫内膜异位症的发病机制之间没有联系。AQP5 的活性被雌激素增加，通过磷脂酰肌醇-3-激酶和蛋白激酶 B（PI3K/AKT），有助于异位子宫内膜的体内植入。在体外，AQP9 参与细胞外信号调节激酶/p38 丝裂原活化蛋白激酶（ERK/p38 MAPK）通路，并通过刺激基质金属蛋白酶（MMP）2 和 MMP9 来帮助迁移和侵袭。ClC-3 也在异位子宫内膜中过度表达，并上调 MMP9。
现有证据表明 CFTR、AQP 和 ClC-3 在子宫内膜异位症发病机制中起关键作用。然而，获得的数据不足以确定离子通道在疾病病因中的直接作用。需要进一步的研究来阐明这种关系。
