Laboratory of Endometrium, Endometriosis & Reproductive Medicine, Department of Development and Regeneration, KU Leuven, Herestraat 49 box 611, 3000 Leuven, Belgium.
Laboratory of Ion Channel Research, Department of Cellular and Molecular Medicine, KU Leuven, VIB Center for Brain & Disease Research, Herestraat 49 box 802, 3000 Leuven, Belgium.
Int J Mol Sci. 2018 Aug 21;19(9):2467. doi: 10.3390/ijms19092467.
Endometriosis is a common gynecological disease that is characterized by the presence of functional endometrial-like lesions in the abdominal cavity. Aside from epithelial cells, these lesions consist of stromal cells that have the capacity to migrate, adhere, proliferate, and induce neuro- and lymphangiogenesis, which allows them to survive at ectopic locations. However, the exact underlying mechanisms that regulate these changes are yet to be elucidated. The common ground of these processes, however, is the second messenger, calcium. In this regard, members of the superfamily of transient receptor potential (TRP) ion channels, which are known to be calcium-permeable and expressed in the endometrium, have emerged as key regulators. Here, we assessed the molecular and functional expression of TRP channels in stromal cells isolated from the eutopic endometrium of endometriosis patients and controls. Using RT-qPCR, high mRNA levels of TRPV2, TRPV4, TRPM4, TRPM7, TRPC1, TRPC3, TRPC4, and TRPC6 were observed in the whole endometrium throughout the menstrual cycle. Additionally, and in line with previous reports of control patients, TRPV2, TRPV4, TRPC1/4, and TRPC6 were present in human endometrial stromal cells (hESC) from endometriosis patients both at the molecular and functional level. Moreover, proliferation and migration assays illustrated that these parameters were not affected in stromal cells from endometriosis patients. Furthermore, comparison between eutopic and ectopic endometrial samples revealed that the RNA expression pattern of TRP channels did not differ significantly. Collectively, although a functional expression of specific ion channels in hESCs was found, their expression did not correlate with endometriosis.
子宫内膜异位症是一种常见的妇科疾病,其特征是在腹腔内存在功能性子宫内膜样病变。除了上皮细胞外,这些病变还包含有迁移、黏附、增殖和诱导神经和淋巴管生成能力的基质细胞,这使它们能够在异位部位存活。然而,调节这些变化的确切潜在机制尚不清楚。然而,这些过程的共同点是第二信使钙。在这方面,已知瞬态受体电位 (TRP) 离子通道超家族的成员是钙渗透性的,并在子宫内膜中表达,它们已成为关键的调节因子。在这里,我们评估了从子宫内膜异位症患者和对照组的在位子宫内膜中分离的基质细胞中 TRP 通道的分子和功能表达。使用 RT-qPCR,在整个月经周期中,整个子宫内膜中 TRPV2、TRPV4、TRPM4、TRPM7、TRPC1、TRPC3、TRPC4 和 TRPC6 的 mRNA 水平均较高。此外,与对照组患者的先前报道一致,TRPV2、TRPV4、TRPC1/4 和 TRPC6 存在于子宫内膜异位症患者的人子宫内膜基质细胞 (hESC) 中,无论是在分子水平还是功能水平。此外,增殖和迁移实验表明,这些参数在子宫内膜异位症患者的基质细胞中不受影响。此外,在位和异位子宫内膜样本的比较表明,TRP 通道的 RNA 表达模式没有显著差异。总的来说,尽管在 hESCs 中发现了特定离子通道的功能性表达,但它们的表达与子宫内膜异位症无关。