CCL19/CCR7 contributes to the pathogenesis of endometriosis via PI3K/Akt pathway by regulating the proliferation and invasion of ESCs

ProblemThe 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.MethodsELISA 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.ResultsPeritoneal 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.ConclusionThese data indicate CCL19/CCR7 contributes to proliferation and invasion of ESCs, which are conducive to the pathogenesis of endometriosis through activating PI3K/Akt pathway.

问题 子宫内膜异位症女性的腹腔液中CCL19水平升高，但CCL19/CCR7在子宫内膜异位症发病机制中的确切作用机制仍不清楚。 方法 采用酶联免疫吸附测定（ELISA）和免疫组化方法分析子宫内膜异位症女性（n = 38）和对照组（n = 32）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间质细胞（ESCs）的增殖和侵袭能力。通过蛋白质印迹法分析Bcl2、MMP2、MMP9和p - AKT/AKT的表达。 结果 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中CCL19浓度明显高于轻微/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水平更高。CCL19通过激活PI3K/Akt信号通路经CCR7显著促进ESCs的增殖和侵袭。CCL19/CCR7相互作用显著增强ESCs中Akt、Bcl2、MMP2和MMP9的磷酸化。 结论 这些数据表明CCL19/CCR7有助于ESCs的增殖和侵袭，通过激活PI3K/Akt通路促进子宫内膜异位症的发病。