Department of Obstetrics and Gynecology, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, Zhejiang Province, People's Republic of China.
Institute of Burn Research, South-West Hospital, State Key Lab of Trauma, Burn and Combined Injury, Chongqing Key Laboratory for Disease Proteomics, Third Military Medical University, Chongqing, China.
Reprod Sci. 2021 Feb;28(2):435-446. doi: 10.1007/s43032-020-00301-8. Epub 2020 Sep 9.
Endometriosis is generally characterized as a tumor-like disease because of its potential for distant metastasis and local tissue invasion, while whether osteopontin (OPN) plays a role in the pathogenesis of endometriosis has not been thoroughly investigated. We investigated the expression of OPN, urokinase plasminogen activator (uPA), phosphatidylinositol 3 kinase (PI3K), and phospho-PI3 kinase (p-PI3K) in endometrial stromal cells (ESCs). The serum concentration of OPN was determined by enzyme-linked immunosorbent assays (ELISA). OPN was downregulated to explore the corresponding change of uPA, p-PI3K, F-actin, and α-tubulin. The expression of OPN, uPA, PI3K, and p-PI3K was evaluated by western blot and quantitative real-time PCR (RT-qPCR) and the expression of F-actin and α-tubulin was confirmed by immunofluorescence assay. The proliferation and migration abilities of ESCs were investigated by CCK8, transwell, and wound scratch assays. Endometrial OPN, p-PI3K, and uPA expressions and serum OPN levels were increased in patients with endometriosis compared with the control. The expressions of p-PI3K, uPA, and α-tubulin were decreased by siRNA-OPN interference in ectopic ESCs. Activation and inhibition of the PI3K pathway apparently upregulate and downregulate uPA expression. Knockdown of OPN and inhibition of the PI3K pathway remarkably inhibited cell migration in ectopic ESCs. Meanwhile, activation of the PI3K pathway promoted the migration ability of ectopic ESCs. OPN may regulate the expression of uPA through the PI3K signal pathway to affect the migration ability of ESCs, indicating that OPN, uPA, and the PI3K pathway may be potential targets for interrupting development of endometriosis.
子宫内膜异位症一般具有肿瘤样特征，因为它具有远处转移和局部组织浸润的潜力，而骨桥蛋白（OPN）是否在子宫内膜异位症的发病机制中起作用尚未得到深入研究。我们研究了子宫内膜基质细胞（ESCs）中 OPN、尿激酶纤溶酶原激活物（uPA）、磷脂酰肌醇 3 激酶（PI3K）和磷酸化 PI3K（p-PI3K）的表达。通过酶联免疫吸附测定（ELISA）测定 OPN 的血清浓度。下调 OPN 以探讨相应的 uPA、p-PI3K、F-肌动蛋白和α-微管蛋白的变化。通过 Western blot 和定量实时 PCR（RT-qPCR）评估 OPN、uPA、PI3K 和 p-PI3K 的表达，并通过免疫荧光法验证 F-肌动蛋白和α-微管蛋白的表达。通过 CCK8、Transwell 和划痕实验研究 ESC 的增殖和迁移能力。与对照组相比，子宫内膜异位症患者的子宫内膜 OPN、p-PI3K 和 uPA 表达和血清 OPN 水平增加。siRNA-OPN 干扰异位 ESC 中 p-PI3K、uPA 和α-微管蛋白的表达降低。PI3K 通路的激活和抑制明显上调和下调 uPA 表达。OPN 敲低和 PI3K 通路抑制明显抑制异位 ESC 的细胞迁移。同时，PI3K 通路的激活促进了异位 ESC 的迁移能力。OPN 可能通过 PI3K 信号通路调节 uPA 的表达，从而影响 ESC 的迁移能力，这表明 OPN、uPA 和 PI3K 通路可能是中断子宫内膜异位症发展的潜在靶点。
Zotero 插件
