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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
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
Type: article (author version)
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)

Submitter: 木村 敦

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