Department of Pharmacy, Affiliated Shenzhen Maternity and Child Healthcare Hospital, Southern Medical University, Shenzhen, Guangdong 518028, P.R. China.
Department of Traditional Chinese Medicine, Affiliated Shenzhen Maternity and Child Healthcare Hospital, Southern Medical University, Shenzhen, Guangdong 518028, P.R. China.
J Microbiol Biotechnol. 2022 Jun 28;32(6):792-799. doi: 10.4014/jmb.2112.12056. Epub 2022 May 17.
As a vital problem in reproductive health, recurrent spontaneous abortion (RSA) affects about 1% of women. We performed this study with an aim to explore the molecular mechanism of interleukin-23 (IL-23) and find optimal or effective methods to improve RSA. First, ELISA was applied to evaluate the expressions of IL-23 and its receptor in HTR-8/SVneo cells after IL-23 treatment. CCK-8, TUNEL, wound healing and transwell assays were employed to assess the proliferation, apoptosis, migration and invasion of HTR-8/SVneo cells, respectively. Additionally, the expressions of apoptosis-, migration-, epithelial-mesenchymal transition- (EMT-) and p38 MAPK signaling pathway-related proteins were measured by western blotting. To further investigate the relationship between IL-23 and p38 MAPK signaling pathway, HTR-8/SVneo cells were treated for 1 h with p38 MAPK inhibitor SB239063, followed by a series of cellular experiments on proliferation, apoptosis, migration and invasion, as aforementioned. The results showed that IL-23 and its receptors were greatly elevated in IL-23-treated HTR-8/SVneo cells. Additionally, IL-23 demonstrated suppressive effects on the proliferation, apoptosis, migration, invasion and EMT of IL-23-treated HTR-8/SVneo cells. More importantly, the molecular mechanism of IL-23 was revealed in this study; that is to say, IL-23 inhibited the proliferation, apoptosis, migration, invasion and EMT of IL-23-treated HTR-8/SVneo cells via activating p38 MAPK signaling pathway. In conclusion, IL-23 inhibits trophoblast proliferation, migration, and EMT via activating p38 MAPK signaling pathway, suggesting that IL-23 might be a novel target for the improvement of RSA.
作为生殖健康的一个重要问题，复发性自然流产（RSA）影响了约 1%的女性。我们进行这项研究的目的是探讨白细胞介素-23（IL-23）的分子机制，并找到改善 RSA 的最佳或有效方法。首先，我们采用 ELISA 法检测 IL-23 处理后 HTR-8/SVneo 细胞中 IL-23 及其受体的表达。采用 CCK-8、TUNEL、划痕愈合和 Transwell 实验分别评估 HTR-8/SVneo 细胞的增殖、凋亡、迁移和侵袭能力。此外，通过 Western blot 法检测凋亡、迁移、上皮间质转化（EMT）和 p38 MAPK 信号通路相关蛋白的表达。为了进一步研究 IL-23 与 p38 MAPK 信号通路的关系，我们用 p38 MAPK 抑制剂 SB239063 处理 HTR-8/SVneo 细胞 1 h，然后进行上述一系列细胞增殖、凋亡、迁移和侵袭实验。结果表明，IL-23 及其受体在 IL-23 处理的 HTR-8/SVneo 细胞中显著升高。此外，IL-23 对 IL-23 处理的 HTR-8/SVneo 细胞的增殖、凋亡、迁移、侵袭和 EMT 具有抑制作用。更重要的是，本研究揭示了 IL-23 的分子机制，即 IL-23 通过激活 p38 MAPK 信号通路抑制 IL-23 处理的 HTR-8/SVneo 细胞的增殖、凋亡、迁移、侵袭和 EMT。总之，IL-23 通过激活 p38 MAPK 信号通路抑制滋养细胞的增殖、迁移和 EMT，提示 IL-23 可能成为改善 RSA 的新靶点。
