Jiang Xinchan, Chen Xiaobo
School of Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou, Guangdong 510006, P.R. China.
Department of Integrated Traditional Chinese and Western Medicine in Metabolic Disease, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, Guangdong 510699, P.R. China.
Exp Ther Med. 2023 Sep 26;26(5):526. doi: 10.3892/etm.2023.12225. eCollection 2023 Nov.
Interleukin (IL)-6 upregulation is involved in the pathogenesis of adenomyosis, but the underlying mechanism remains to be elucidated. Exosomes mediate intercellular communication, therefore the present study investigated whether endometrial cell-derived exosomes mediated the crosstalk between the endometrium and the myometrium via IL-6 signaling. Primary adenomyotic myometrial (AM) cells and eutopic endometrial cells were isolated from patients with adenomyosis. Exosomes were obtained from endometrial cells and incubated with AM cells in the presence or absence of tocilizumab (an IL-6 inhibitor). MTT, flow cytometry and wound-healing assays were performed to examine AM cell proliferation, apoptosis, cell cycle distribution and migration. Western blotting and reverse transcription-quantitative PCR were conducted to determine the expression of the IL-6/Janus kinase 2 (JAK2)/STAT3 pathway proteins. Incubation with endometrial cell exosomes suppressed cell apoptosis of AM cells compared with controls, accompanied by increases in IL-6 production and JAK2/STAT3 phosphorylation. Endometrial cell exosomes promoted cell proliferation, increased the percentage of S-phase cells and enhanced the migration of AM cells. These effects were completely reversed by tocilizumab, along with substantial decreases in IL-6 production and JAK2/STAT3 phosphorylation. Endometrial cell-derived exosomes promote cell proliferation, migration and cell cycle transition of AM cells through IL-6/JAK2/STAT3 activation, facilitating the development of adenomyosis by mediating the crosstalk between the endometrium and the myometrium, and IL-6 targeted therapy could be a complementary approach against adenomyosis.
白细胞介素（IL）-6上调参与子宫腺肌病的发病机制，但其潜在机制仍有待阐明。外泌体介导细胞间通讯，因此本研究调查了子宫内膜细胞来源的外泌体是否通过IL-6信号介导子宫内膜与子宫肌层之间的相互作用。从子宫腺肌病患者中分离出原发性子宫腺肌病肌层（AM）细胞和在位内膜细胞。从子宫内膜细胞中获得外泌体，并在有或没有托珠单抗（一种IL-6抑制剂）的情况下与AM细胞一起孵育。进行MTT、流式细胞术和伤口愈合试验以检测AM细胞增殖、凋亡、细胞周期分布和迁移。进行蛋白质印迹和逆转录-定量PCR以确定IL-6/Janus激酶2（JAK2）/信号转导和转录激活因子3（STAT3）通路蛋白的表达。与对照组相比，用子宫内膜细胞外泌体孵育可抑制AM细胞的凋亡，同时IL-6产生和JAK2/STAT3磷酸化增加。子宫内膜细胞外泌体促进细胞增殖，增加S期细胞百分比并增强AM细胞的迁移。托珠单抗完全逆转了这些作用，同时IL-6产生和JAK2/STAT3磷酸化大幅降低。子宫内膜细胞来源的外泌体通过激活IL-6/JAK2/STAT3促进AM细胞的增殖、迁移和细胞周期转变，通过介导子宫内膜与子宫肌层之间的相互作用促进子宫腺肌病的发展，并且IL-6靶向治疗可能是对抗子宫腺肌病的一种补充方法。
