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Mifepristone increases AQP1 mRNA expression, angiogenesis, and cell permeability through the ERK MAPK pathway

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Abstract

Aims

The purpose of this study was to investigate the mechanism of mifepristone serves as an anti-implantation contraceptive drug on aquaporins 1 (AQP1) expression.

Methods

Human umbilical vein endothelial cells (HUVECs) were used to detect the effects of different concentrations of mifepristone (0, 0.065, 0.2, and 1 μmol/L) on the activity of angiogenesis and AQP1 expression. The expression of AQP1 was tested by the real-time PCR. The angiogenesis and penetration function of HUVECs was investigated by Matrigel lumen formation and trans-well assay, respectively.

Results

The expression of AQP1, angiogenesis and cell permeability were significantly higher than control groups in HUVECs treatment with mifepristone at 1 μmol/L for 12 h. Estrogen and progesterone decreased the up-regulation of AQP1 and cell permeability, not angiogenesis, induced by mifepristone. Mifepristone increased protein levels of p-ERK, not p-p38 or p-JNK, and pre-treatment with ERK MAPK-specific inhibitor significantly inhibited the up-regulation of AQP1 mRNA expression, angiogenesis and cell permeability induced by mifepristone. si-AQP1 significantly reduced the up-regulation of angiogenesis, cell permeability and p-ERK/ERK ratio expression induced by mifepristone treatment. Overexpression of AQP1 enhanced the increase of expression ratio of p-ERK/ERK induced by mifepristone.

Conclusions

Low-dose mifepristone increased cell permeability, angiogenesis and AQP1 expression, which was involved in MAPK pathways. This provides new insights into the molecular mechanism of mifepristone serves as an anti-implantation contraceptive drug.

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Acknowledgements

Not applicable.

Funding

Funding was provided by National Natural Science Foundation of China (Grant No.: 81701502).

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Author notes

  1. Wenwen Wang, Yuanyuan Kang these authors are contributed equally to this work.

Authors and Affiliations

  1. Department of Pathology, Women’s Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, Zhejiang Province, China

    Wenwen Wang & Feng Zhou

  2. Department of Pharmacology, Zhejiang University School of Medicine, Hangzhou, 310058, China

    Yuanyuan Kang & Yu Jiang

  3. Department of Gynecology, Women’s Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, China

    Yalin Zhuang

  4. National Clinical Research Center for Child Health, National Children’s Regional Medical Center, the Children’s Hospital, Zhejiang University School of Medicine, Hangzhou, 310052, China

    Gensheng Zhang

  5. Department of Reproductive Medicine Center, Zhongshan City People’s Hospital, Zhongshan, 528403, China

    Yuezhou Chen

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  1. Wenwen Wang
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Correspondence to Yuezhou Chen or Feng Zhou.

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Wang, W., Kang, Y., Jiang, Y. et al. Mifepristone increases AQP1 mRNA expression, angiogenesis, and cell permeability through the ERK MAPK pathway. Mol Biol Rep 50, 1069–1077 (2023). https://doi.org/10.1007/s11033-022-08082-w

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  • DOI: https://doi.org/10.1007/s11033-022-08082-w

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