LIM Kinase 1 Mediates Estradiol Effects on the Phosphorylation of Cofilin1 in Eutopic Endometrial Stromal Cells During the Invasion and Proliferation of Endometriosis
LIM Kinase 1 Mediates Estradiol Effects on the Phosphorylation of Cofilin1 in Eutopic Endometrial Stromal Cells During the Invasion and Proliferation of Endometriosis
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LIM激酶1介导子宫内膜异位症侵袭和增殖过程中雌二醇对在位子宫内膜基质细胞Cofilin1磷酸化的影响
DOI：
10.1177/1933719119828076
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发表时间：
2019-11-01
影响因子：
2.9
通讯作者：
Wang, Danbo
中科院分区：
文献类型：
--
作者：
Liu, Jing;Zhang, Zhifang;Wang, Danbo
子宫内膜异位症是一种雌激素依赖型妇科疾病；然而，雌二醇促进子宫内膜异位症发展的机制，包括侵袭和增殖，尚不清楚。雌二醇通过调节细胞骨架参与细胞的侵袭和增殖。与正常异位子宫内膜细胞相比，细胞骨架调节因子（LIM激酶1 [LIMK1]和cofilin1）的异常高表达与子宫内膜异位症患者异位子宫内膜间质细胞的侵袭性和增殖性增加密切相关。本研究的目的是分析雌二醇通过LIMK1/cofilin1通路在子宫内膜异位症女性子宫内膜侵袭和增殖中的作用。为了解决这个问题，我们从子宫内膜异位症患者的子宫中分离出原发性异位子宫内膜基质细胞，并在不添加雌二醇的情况下进行培养。western blotting分析cofilin1的磷酸化。通过RNA干扰技术对LIMK1敲除后的细胞侵袭性和增殖进行评估。我们发现，在LIMK1沉默前，接受雌二醇治疗的子宫内膜异位症患者异位子宫内膜基质细胞cofilin1和LIMK1的磷酸化水平均高于未接受雌二醇治疗的细胞（P < 0.05和P < 0.01）。cofilin1和LIMK1蛋白的总水平没有变化（P < 0.05和P < 0.05）。LIMK1沉默后，雌二醇对cofilin1的磷酸化水平明显降低，侵袭性和增殖明显降低（P < 0.05和P < 0.05）。由此可见，雌二醇对cofilin1的磷酸化是由LIMK1介导的，雌二醇通过LIMK1/cofilin1通路参与调节子宫内膜异位症患者细胞的侵袭和增殖。
Endometriosis is an estrogen-dependent gynecological disease; however, the mechanism by which estradiol promotes the development of endometriosis, including invasion and proliferation, remains unclear. Estradiol is involved in cell invasion and proliferation by regulating the cytoskeleton. The abnormally high expression of cytoskeletal regulators (LIM kinase 1 [LIMK1] and cofilin1) is closely related to increased invasiveness and proliferation of eutopic endometrial stromal cells from endometriosis patients compared to normal eutopic endometrial cells. The aim of this study was to analyze the role of estradiol during invasion and proliferation through the LIMK1/cofilin1 pathway in the endometrium of women with endometriosis. To address this, primary eutopic endometrial stromal cells were isolated from the uteri of patients with endometriosis and cultured without estradiol. The phosphorylation of cofilin1 was analyzed by western blotting. Cell invasiveness and proliferation were evaluated following LIMK1 knockdown by RNA interference technology. We found that, before LIMK1silencing, the phosphorylation levels of cofilin1 and LIMK1 of eutopic endometrial stromal cells from endometriosis patients treated with estradiol were higher than cells not treated with estradiol (P < .05 and P < .01, respectively). The total levels of cofilin1 and LIMK1 protein did not change (P > .05 and P > .05, respectively). After LIMK1 silencing, the phosphorylation of cofilin1 by estradiol was significantly reduced, and invasiveness and proliferation were clearly and concurrently decreased (P < .05 and P < .05, respectively). Thus, the phosphorylation of cofilin1 by estradiol is mediated by LIMK1, and estradiol is involved in regulating cell invasion and proliferation in endometriotic patients through the LIMK1/cofilin1 pathway.