Department of Laboratory Medicine, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai 200040, P.R. China.
Phase I Clinical Trial Unit, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200336, P.R. China.
Mol Med Rep. 2022 Feb;25(2). doi: 10.3892/mmr.2021.12573. Epub 2021 Dec 16.
Endometriosis (EM), the presence of functional endometrial glands and stroma outside the uterine cavity, is a common gynecological disorder. At present, the pathogenesis of EM has not been fully elucidated, so there is still a lack of effective therapy. The present study aimed to explore the role of C‑C motif chemokine ligand 28 (CCL28) and its underlying mechanism in endometrial stromal cells to propose a novel therapy for EM treatment. The expression of CCL28 and CC chemokine receptor 10 (CCR10) were examined. After CCL28 knockdown or overexpression by lentivirus infection, cell proliferation and invasion were measured. It was revealed that compared with normal, the expression levels of CCL28 and CCR10 were significantly elevated in endometrial tissues of patients with EM. Knockdown of CCL28 in endometrial stromal cells significantly suppressed cell proliferation and invasion, and this was accompanied by significantly reduced expression levels of CCR10, MMP2, MMP9, integrin β1 (ITGB1) and phosphorylated (p)‑ERK/ERK ratio. The addition of the CCL28 recombinant protein had an opposite effect to CCL28 downregulation. Furthermore, the ERK inhibitor, PD98059, reduced CCL28‑induced cell proliferation and invasion, as well as the expression levels of MMP2, MMP9, ITGB1 and p‑ERK. Therefore, the present study indicated that CCL28 may contribute to the progression of EM by regulating MMP2, MMP9 and ITGB1 expression and function via the activation of the ERK signaling pathway.
子宫内膜异位症（EM）是指功能活性的子宫内膜腺体和基质出现在子宫腔外的一种常见妇科疾病。目前，EM 的发病机制尚未完全阐明，因此仍然缺乏有效的治疗方法。本研究旨在探讨 C-C 基序趋化因子配体 28（CCL28）及其在子宫内膜基质细胞中的潜在作用机制，为 EM 的治疗提供一种新的治疗方法。检测 CCL28 和 CC 趋化因子受体 10（CCR10）的表达。通过慢病毒感染敲低或过表达 CCL28 后，测量细胞增殖和侵袭能力。结果表明，与正常组相比，EM 患者的子宫内膜组织中 CCL28 和 CCR10 的表达水平明显升高。敲低子宫内膜基质细胞中的 CCL28 显著抑制细胞增殖和侵袭，同时 CCR10、MMP2、MMP9、整合素 β1（ITGB1）和磷酸化（p）-ERK/ERK 比值的表达水平显著降低。CCL28 重组蛋白的添加与 CCL28 下调的作用相反。此外，ERK 抑制剂 PD98059 降低了 CCL28 诱导的细胞增殖和侵袭，以及 MMP2、MMP9、ITGB1 和 p-ERK 的表达水平。因此，本研究表明 CCL28 可能通过激活 ERK 信号通路调节 MMP2、MMP9 和 ITGB1 的表达和功能，从而促进 EM 的进展。
