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Mouse prolyl oligopeptidase plays a role in trophoblast stem cell differentiation into trophoblast giant cell and spongiotrophoblast
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Title: | Mouse prolyl oligopeptidase plays a role in trophoblast stem cell differentiation into trophoblast giant cell and spongiotrophoblast |
Authors: | Maruyama, Yuki Browse this author | Matsubara, Shin Browse this author | Kimura, Atsushi P. Browse this author →KAKEN DB |
Keywords: | Prolyl endopeptidase | SUAM-14746 | Placenta | Protease |
Issue Date: | May-2017 |
Publisher: | Elsevier |
Journal Title: | Placenta |
Volume: | 53 |
Start Page: | 8 |
End Page: | 15 |
Publisher DOI: | 10.1016/j.placenta.2017.03.004 |
PMID: | 28487025 |
Abstract: | Introduction: Prolyl oligopeptidase (prolyl endopeptidase, Prep), a multifunctional protease hydrolyzing -Pro-X-peptide bonds, is highly expressed in the mouse placenta, but the function during development is not known. We explored the possibility of Prep's involvement in placental differentiation. Methods: We cultured trophoblast stem cells (TSCs) derived from the E6.5 mouse embryo and investigated the detailed expression pattern of Prep during their differentiation. Prep-specific inhibitors were added to the TSC culture, and the effect on the differentiation was assessed by microscopic observation and the expression of marker gene for each placental cell. Results: During TSC differentiation for 6 days, Prep was constantly detected at mRNA, protein, and activity levels, and the proteinwas found mainly in the cytoplasm. The addition of 30 mu M and 10 mu M SUAM-14746, a Prep-specific inhibitor, effectively inhibited the differentiation into spongiotrophoblasts (SpTs) and trophoblast giant cells (TGCs), while the TSC viability was not affected. 5 mu M SUAM-14746 impaired the differentiation into SpTs, and 1 mu M SUAM-14746 exhibited no effects. Another Prep-specific inhibitor, KYP-2047, did not affect the differentiation. We confirmed efficient inhibition of Prep enzymatic activity in TSCs by both inhibitors. Conclusion: The dose-dependent effect of SUAM-14746 on TSCs suggests that Prep plays an important role in the differentiation into SpTs and TGCs in the mouse placenta. (C) 2017 Elsevier Ltd. All rights reserved. |
Rights: | © 2017 This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ | http://creativecommons.org/licenses/by-nc-nd/4.0/ |
Type: | article (author version) |
URI: | http://hdl.handle.net/2115/68461 |
Appears in Collections: | 理学院・理学研究院 (Graduate School of Science / Faculty of Science) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 木村 敦
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