Centre of Reproductive Medicine, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen, China.
Department of Obstetrics and Gynecology, Peking University Shenzhen Hospital, Shenzhen, China.
Am J Reprod Immunol. 2017 Nov;78(5). doi: 10.1111/aji.12744. Epub 2017 Aug 30.
The level of CCL19 increased in the peritoneal fluid of women with endometriosis, but the precise mechanism of CCL19/CCR7 in the pathogenesis of endometriosis remains unknown.
ELISA and immunohistochemistry were performed to analyze CCL19/CCR7 expressions in peritoneal fluid and endometrium from women with endometriosis (n = 38) and controls (n = 32). Cell proliferation and transwell invasion assays were applied to detect proliferation and invasion of human endometrial stromal cells (ESCs). Expressions of Bcl2, MMP2, MMP9, and p-AKT/AKT were analyzed by Western blot.
Peritoneal fluid concentration of CCL19 in patients with endometriosis was higher than that in controls. Those patients with moderate/severe endometriosis had significantly higher peritoneal fluid concentrations of CCL19 compared to those with minimal/mild endometriosis. Higher CCL19 and CCR7 were found in the endometrium with endometriosis compared to control. CCL19 significantly enhanced ESC proliferation and invasion through CCR7 via activating PI3K/Akt signal pathways. CCL19/CCR7 interaction significantly enhanced phosphorylation of Akt, Bcl2, MMP2, and MMP9 in ESCs.
These data indicate CCL19/CCR7 contributes to proliferation and invasion of ESCs, which are conducive to the pathogenesis of endometriosis through activating PI3K/Akt pathway.
子宫内膜异位症患者腹腔液中 CCL19 水平升高，但 CCL19/CCR7 在子宫内膜异位症发病机制中的确切机制尚不清楚。
采用 ELISA 和免疫组织化学法分析 38 例子宫内膜异位症患者（病例组）和 32 例对照者（对照组）腹腔液和子宫内膜中 CCL19/CCR7 的表达。应用细胞增殖和 Transwell 侵袭实验检测人子宫内膜基质细胞（ESCs）的增殖和侵袭。采用 Western blot 分析 Bcl2、MMP2、MMP9 和 p-AKT/AKT 的表达。
子宫内膜异位症患者腹腔液中 CCL19 浓度高于对照组。中重度子宫内膜异位症患者腹腔液 CCL19 浓度明显高于轻度/极轻度子宫内膜异位症患者。与对照组相比，子宫内膜异位症患者的子宫内膜中 CCL19 和 CCR7 表达更高。CCL19 通过激活 PI3K/Akt 信号通路，通过 CCR7 显著增强 ESC 的增殖和侵袭。CCL19/CCR7 相互作用显著增强了 ESCs 中 Akt、Bcl2、MMP2 和 MMP9 的磷酸化。
这些数据表明，CCL19/CCR7 有助于 ESCs 的增殖和侵袭，通过激活 PI3K/Akt 通路有利于子宫内膜异位症的发病机制。
