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褪黑素抑制 17β-雌二醇诱导的正常和子宫内膜异位症子宫内膜上皮细胞的迁移、侵袭和上皮-间充质转化。

Melatonin inhibits 17β-estradiol-induced migration, invasion and epithelial-mesenchymal transition in normal and endometriotic endometrial epithelial cells.

机构信息

Center for Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, 250021, People's Republic of China.

National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Jinan, 250021, People's Republic of China.

出版信息

Reprod Biol Endocrinol. 2018 Jun 23;16(1):62. doi: 10.1186/s12958-018-0375-5.

DOI:10.1186/s12958-018-0375-5
PMID:29935526
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6015458/
Abstract

BACKGROUND

Melatonin is a potential therapeutic agent for endometriosis, but its molecular mechanism is unclear. Here, we investigated the effect of melatonin on the epithelial-mesenchymal transition (EMT) in endometriotic endometrial epithelial cells and explored the pathway that might be involved.

METHODS

This hospital-based study included 60 women of reproductive age using the endometrium for immunohistochemistry, 6 women of reproductive age undergoing bilateral tubal ligation and 6 patients with endometriosis for isolation of endometrial epithelial cells or subsequent analysis, respectively. We examined the expression of Notch1/Numb signaling and EMT markers by immunohistochemistry analysis and western blot analysis, the invasion and migration of endometrial epithelial cells by transwell assays, and the cell proliferation by CCK8 assays.

RESULTS

Compared with normal endometrium, the endometriotic eutopic endometrium showed increased expression of Notch1, Slug, Snail, and N-cadherin, and decreased expression of E-cadherin and Numb. Melatonin or Notch inhibition by specific inhibitor blocked 17β-estradiol-induced cell proliferation, invasion, migration and EMT-related markers in both normal and endometriotic epithelial cells.

CONCLUSIONS

Our data suggest that aberrant expression of Notch1/Numb signaling and the EMT is present in endometriotic endometrium. Melatonin may block 17β-estradiol-induced migration, invasion and EMT in normal and endometriotic epithelial cells by upregulating Numb expression and decreasing the activity of the Notch signaling pathway.

摘要

背景

褪黑素可能是子宫内膜异位症的一种潜在治疗药物，但它的分子机制尚不清楚。在这里，我们研究了褪黑素对子宫内膜异位症子宫内膜上皮细胞上皮-间充质转化（EMT）的影响，并探讨了可能涉及的途径。

方法

这项基于医院的研究包括 60 名处于生育期的女性，她们的子宫内膜用于免疫组织化学分析，6 名处于生育期的女性接受双侧输卵管结扎术，6 名子宫内膜异位症患者分别用于分离子宫内膜上皮细胞或随后的分析。我们通过免疫组织化学分析和 Western blot 分析检查了 Notch1/Numb 信号和 EMT 标志物的表达、子宫内膜上皮细胞的侵袭和迁移通过 Transwell 测定，以及通过 CCK8 测定细胞增殖。

结果

与正常子宫内膜相比，子宫内膜异位症的在位子宫内膜中 Notch1、Slug、Snail 和 N-钙黏蛋白的表达增加，而 E-钙黏蛋白和 Numb 的表达减少。褪黑素或 Notch 特异性抑制剂阻断 17β-雌二醇诱导的正常和子宫内膜异位症上皮细胞的细胞增殖、侵袭、迁移和 EMT 相关标志物。

结论

我们的数据表明，Notch1/Numb 信号和 EMT 的异常表达存在于子宫内膜异位症的子宫内膜中。褪黑素可能通过上调 Numb 表达和降低 Notch 信号通路的活性来阻断 17β-雌二醇诱导的正常和子宫内膜异位症上皮细胞的迁移、侵袭和 EMT。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7bb0/6015458/cbe97f8c8aa0/12958_2018_375_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7bb0/6015458/f05628bacbaf/12958_2018_375_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7bb0/6015458/47b0c0d26ee5/12958_2018_375_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7bb0/6015458/0e32a93623ad/12958_2018_375_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7bb0/6015458/a0be162c8dc1/12958_2018_375_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7bb0/6015458/233d92be1615/12958_2018_375_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7bb0/6015458/2e8883d6aa7b/12958_2018_375_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7bb0/6015458/cd730813c697/12958_2018_375_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7bb0/6015458/cbe97f8c8aa0/12958_2018_375_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7bb0/6015458/f05628bacbaf/12958_2018_375_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7bb0/6015458/47b0c0d26ee5/12958_2018_375_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7bb0/6015458/0e32a93623ad/12958_2018_375_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7bb0/6015458/a0be162c8dc1/12958_2018_375_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7bb0/6015458/233d92be1615/12958_2018_375_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7bb0/6015458/2e8883d6aa7b/12958_2018_375_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7bb0/6015458/cd730813c697/12958_2018_375_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7bb0/6015458/cbe97f8c8aa0/12958_2018_375_Fig8_HTML.jpg

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