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IL-23 Inhibits Trophoblast Proliferation, Migration, and EMT via Activating p38 MAPK Signaling Pathway to Promote Recurrent Spontaneous Abortion

  • He, Shan (Department of Pharmacy, Affiliated Shenzhen Maternity and Child Healthcare Hospital, Southern Medical University) ;
  • Ning, Yan (Department of Traditional Chinese Medicine, Affiliated Shenzhen Maternity and Child Healthcare Hospital, Southern Medical University) ;
  • Ma, Fei (Department of Traditional Chinese Medicine, Affiliated Shenzhen Maternity and Child Healthcare Hospital, Southern Medical University) ;
  • Liu, Dayan (Department of Genesiology, Affiliated Shenzhen Maternity and Child Healthcare Hospital, Southern Medical University) ;
  • Jiang, Shaoyan (Department of Pharmacy, Affiliated Shenzhen Maternity and Child Healthcare Hospital, Southern Medical University) ;
  • Deng, Shaojie (Department of Pharmacy, Affiliated Shenzhen Maternity and Child Healthcare Hospital, Southern Medical University)
  • Received : 2022.01.03
  • Accepted : 2022.05.13
  • Published : 2022.06.28

Abstract

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.

Keywords

Acknowledgement

This work was supported by grants from the National Nature Science Foundation (82104576), the Basic andApplied Basic Research Fund of Guangdong Province (2019A1515110579), the Scientific Research Project of Guangdong Bureau of Traditional Chinese Medicine (20201292), Shenzhen Science Technology and Innovation Committee (JCYJ20210324130012031 and JCYJ20210324130013033) and the Sanming Project of Medicine inShenzhen (SZSM201612046).

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