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High dose of baicalin or baicalein can reduce tight junction integrity by partly targeting the first PDZ domain of zonula occludens-1 (ZO-1)
http://hdl.handle.net/2237/00033489
http://hdl.handle.net/2237/0003348933cc2fae-b47d-403d-8264-99870ab5c5b8
名前 / ファイル | ライセンス | アクション |
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Item type | 学術雑誌論文 / Journal Article(1) | |||||
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公開日 | 2021-02-08 | |||||
タイトル | ||||||
タイトル | High dose of baicalin or baicalein can reduce tight junction integrity by partly targeting the first PDZ domain of zonula occludens-1 (ZO-1) | |||||
言語 | en | |||||
著者 |
Hisada, Misaki
× Hisada, Misaki× Hiranuma, Minami× Nakashima, Mio× Goda, Natsuko× Tenno, Takeshi× Hiroaki, Hidekazu |
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アクセス権 | ||||||
アクセス権 | open access | |||||
アクセス権URI | http://purl.org/coar/access_right/c_abf2 | |||||
権利 | ||||||
権利情報 | © 2020. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | PDZ domain Inhibitor | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | Tight junction | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | Zonula occludens-1 | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | NMR | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | Baicalin | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | Absorption enhancer | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | TGF-β signaling pathway | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | Epithelial cell barrier | |||||
抄録 | ||||||
内容記述 | The tight junction (TJ) is the apical-most intercellular junction complex, serving as a biological barrier of intercellular spaces between epithelial cells. The TJ's integrity is maintained by a key protein–protein interaction between C-terminal motifs of claudins (CLDs) and the postsynaptic density 95 (PSD-95)/discs large/zonula occludens 1 (ZO-1; PDZ) domains of ZO-1. Weak but direct interaction of baicalin and its aglycon, baicalein—which are pharmacologically active components of Chinese skullcap (Radix scutellariae)—with ZO-1(PDZ1) have been observed in NMR experiments. Next, we observed TJ-mitigating activity of these flavonoids against Madin-Darby canine kidney (MDCK) II cells with the downregulation of subcellular localization of CLD-2 at TJs. Meanwhile, baicalein—but not baicalin—induced a slender morphological change of MDCK cells' shape from their normal cobblestone-like shapes. Since baicalin and baicalein did not induce a localization change of occludin (OCLN), a “partial” epithelial–mesenchymal transition (EMT) induced by these flavonoids was considered. SB431542, an ALK-5 inhibitor, reversed the CLD-2 downregulation of both baicalin and baicalein, while SB431542 did not reverse the slender morphology. In contrast, the MEK/ERK inhibitor U0126 reversed the slender shape change. Thus, in addition to inhibition of the ZO-1–CLD interaction, activation of both transforming growth factor-β (TGF-β) and MEK/ERK signaling pathways have been suggested to be involved in TJ reduction by these flavonoids. Finally, we demonstrated that baicalin enhanced the permeability of fluorescence-labeled insulin via the paracellular pathway of the Caco-2 cell layer. We propose that baicalin, baicalein, and Radix scutellariae extract are useful as drug absorption enhancers. | |||||
言語 | en | |||||
内容記述タイプ | Abstract | |||||
内容記述 | ||||||
内容記述 | ファイル公開:2021-11-15 | |||||
言語 | ja | |||||
内容記述タイプ | Other | |||||
出版者 | ||||||
言語 | en | |||||
出版者 | Elsevier | |||||
言語 | ||||||
言語 | eng | |||||
資源タイプ | ||||||
資源タイプresource | http://purl.org/coar/resource_type/c_6501 | |||||
タイプ | journal article | |||||
出版タイプ | ||||||
出版タイプ | AM | |||||
出版タイプResource | http://purl.org/coar/version/c_ab4af688f83e57aa | |||||
DOI | ||||||
関連タイプ | isVersionOf | |||||
識別子タイプ | DOI | |||||
関連識別子 | https://doi.org/10.1016/j.ejphar.2020.173436 | |||||
ISSN(print) | ||||||
収録物識別子タイプ | PISSN | |||||
収録物識別子 | 0014-2999 | |||||
書誌情報 |
en : European Journal of Pharmacology 巻 887, p. 173436, 発行日 2020-11-15 |
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著者版フラグ | ||||||
値 | author |