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  1. D400 創薬科学研究科
  2. D400a 雑誌掲載論文
  3. 学術雑誌

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/2237/00033489
33cc2fae-b47d-403d-8264-99870ab5c5b8
名前 / ファイル ライセンス アクション
EJP-53411R3-accepted-NUrepository.pdf EJP-53411R3-accepted-NUrepository (1.1 MB)
Item type 学術雑誌論文 / Journal Article(1)
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

WEKO 103279

en Hisada, Misaki

Search repository
Hiranuma, Minami

× Hiranuma, Minami

WEKO 103280

en Hiranuma, Minami

Search repository
Nakashima, Mio

× Nakashima, Mio

WEKO 103281

en Nakashima, Mio

Search repository
Goda, Natsuko

× Goda, Natsuko

WEKO 103282

en Goda, Natsuko

Search repository
Tenno, Takeshi

× Tenno, Takeshi

WEKO 103283

en Tenno, Takeshi

Search repository
Hiroaki, Hidekazu

× Hiroaki, Hidekazu

WEKO 103284

en Hiroaki, Hidekazu

Search repository
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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