Department of Obstetrics and Gynecology, Women's Hospital, Zhejiang University School of Medicine, Hangzhou; Department of Obstetrics and Gynecology, Huangyan Hospital of Wenzhou Medical University, Taizhou First People's Hospital, Taizhou.
Department of Obstetrics and Gynecology, Women's Hospital, Zhejiang University School of Medicine, Hangzhou.
Eur J Histochem. 2024 Aug 6;68(3):4052. doi: 10.4081/ejh.2024.4052.
Endometriosis is an estrogen-dependent inflammatory gynecological disease whose pathogenesis is unclear. C-C motif chemokine ligand 18 (CCL18), a chemokine, is involved in several inflammatory diseases. In this study, we aimed to investigate the role of CCL18 in endometriosis and its underlying mechanisms. Human endometrium and peritoneal fluid were obtained from women with and without endometriosis for molecular studies. The expression level of CCL18 in each tissue sample was examined by RNA sequencing analysis, quantitative PCR analysis and immunohistochemistry staining. The effects of CCL18 on cell migration, tube formation and neurite growth were investigated in vitro using primary endometrial cells, human umbilical vein endothelial cells (HUVECs) and dorsal root ganglion (DRG) neurons, respectively. Moreover, the development of endometriosis in mice was studied in vivo by blocking CCL18. CCL18 was shown to be overexpressed in endometrial foci and peritoneal fluid in women with endometriosis and was positively correlated with endometriosis pain. In vitro, CCL18 promoted the migration of ectopic endometrial cells, tube formation of HUVECs, and nerve outgrowth of DRG neurons. More importantly, inhibition of CCL18 significantly suppressed lesion development, angiogenesis, and nerve infiltration in a mouse model of endometriosis. In conclusion, CCL18 may play a role in the progression of endometriosis by increasing endometrial cell migration and promoting neuroangiogenesis.
子宫内膜异位症是一种雌激素依赖性炎症性妇科疾病，其发病机制尚不清楚。趋化因子 C-C 基序配体 18（CCL18）是一种趋化因子，参与多种炎症性疾病。在本研究中，我们旨在研究 CCL18 在子宫内膜异位症中的作用及其潜在机制。我们从患有和不患有子宫内膜异位症的女性中获取子宫内膜和腹腔液样本，用于分子研究。通过 RNA 测序分析、定量 PCR 分析和免疫组织化学染色，检测每个组织样本中 CCL18 的表达水平。我们分别使用原代子宫内膜细胞、人脐静脉内皮细胞（HUVEC）和背根神经节（DRG）神经元，在体外研究 CCL18 对细胞迁移、管形成和神经突生长的影响。此外，我们通过阻断 CCL18 研究了体内小鼠子宫内膜异位症的发展。结果表明，CCL18 在患有子宫内膜异位症的女性的子宫内膜病灶和腹腔液中过表达，并且与子宫内膜异位症疼痛呈正相关。在体外，CCL18 促进异位子宫内膜细胞的迁移、HUVEC 的管形成和 DRG 神经元的神经突生长。更重要的是，CCL18 的抑制显著抑制了子宫内膜异位症小鼠模型中病变的发展、血管生成和神经浸润。总之，CCL18 可能通过增加子宫内膜细胞迁移和促进神经血管生成在子宫内膜异位症的进展中发挥作用。
