High-Expression of Neuropilin 1 Correlates to Estrogen-Induced Epithelial-Mesenchymal Transition of Endometrial Cells in Adenomyosis

Epithelial-mesenchymal transition (EMT) induced by estrogen contributes to the development of adenomyosis. However, the exact underlying mechanism remains mostly obscure. We hypothesized that a transmembrane glycoprotein neuropilin 1 (NRP1) was critical in the EMT induced by estrogen, accelerating the development of adenomyosis. We firstly investigated the expression pattern of NRP1 in endometrium samples from women with adenomyosis. We found that NRP1 expression was significantly increased in the endometrium of uterine adenomyosis, especially in the ectopic endometrium. To determine the role of NRP1 in the EMT in endometrial cells, we used an NRP1 overexpression retrovirus to up-regulate the NPR1 expression in human endometrial cells (HEC-1-A). Endometrial cells infected with NRP1 retroviruses showed a high expression of NRP1 and exerted a mesenchymal phenotype, characterized by down-regulation of E-cadherin and Occludin, up-regulation of α-SMA and N-cadherin, and enhanced migration. Then, we found that 17β-estradiol (E2) up-regulated the expression of NRP1 in endometrial cells in a dose-dependent manner, which was eliminated by raloxifene, a selective estrogen receptor inhibitor. Importantly, NRP1 shRNA significantly suppressed the EMT induced by E2 in endometrial cells. And NRP1 shRNA significantly inhibited the phosphorylation of Smad3 and restored the expressions of Slug and Snail1 mRNA. Collectively, these data highlight the possible role of NRP1 in the EMT in the development of adenomyosis and provide a potential therapeutic target for adenomyosis patients. Similar content being viewed by others

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RH, CZ, and GQP analyzed the data. YPL contributed reagents/materials/analysis tools. RH wrote the paper. YPL critically reviewed the manuscript. All authors had final approval of the submitted versions. Corresponding author Ethics declarations Conflict of Interest The authors declare that they have no conflict of interest. Rights and permissions About this article Cite this article Hu, R., Peng, GQ., Ban, DY. et al. High-Expression of Neuropilin 1 Correlates to Estrogen-Induced Epithelial-Mesenchymal Transition of Endometrial Cells in Adenomyosis. Reprod. Sci. 27, 395–403 (2020). https://doi.org/10.1007/s43032-019-00035-2 Received: Accepted: Published: Version of record: Issue date: DOI: https://doi.org/10.1007/s43032-019-00035-2