{"_buckets": {"deposit": "32cccc72-8bc7-4a36-9b0a-7f041040a26f"}, "_deposit": {"id": "31309", "owners": [], "pid": {"revision_id": 0, "type": "depid", "value": "31309"}, "status": "published"}, "_oai": {"id": "oai:nagoya.repo.nii.ac.jp:00031309"}, "item_10_biblio_info_6": {"attribute_name": "\u66f8\u8a8c\u60c5\u5831", "attribute_value_mlt": [{"bibliographicIssueDates": {"bibliographicIssueDate": "2020-11-15", "bibliographicIssueDateType": "Issued"}, "bibliographicPageStart": "173436", "bibliographicVolumeNumber": "887", "bibliographic_titles": [{"bibliographic_title": "European Journal of Pharmacology"}]}]}, "item_10_description_4": {"attribute_name": "\u6284\u9332", "attribute_value_mlt": [{"subitem_description": "The tight junction (TJ) is the apical-most intercellular junction complex, serving as a biological barrier of intercellular spaces between epithelial cells. The TJ\u0027s integrity is maintained by a key protein\u2013protein 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\u2014which are pharmacologically active components of Chinese skullcap (Radix scutellariae)\u2014with 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\u2014but not baicalin\u2014induced a slender morphological change of MDCK cells\u0027 shape from their normal cobblestone-like shapes. Since baicalin and baicalein did not induce a localization change of occludin (OCLN), a \u201cpartial\u201d epithelial\u2013mesenchymal 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\u2013CLD interaction, activation of both transforming growth factor-\u03b2 (TGF-\u03b2) 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.", "subitem_description_type": "Abstract"}]}, "item_10_description_5": {"attribute_name": "\u5185\u5bb9\u8a18\u8ff0", "attribute_value_mlt": [{"subitem_description": "\u30d5\u30a1\u30a4\u30eb\u516c\u958b\uff1a2021-11-15", "subitem_description_type": "Other"}]}, "item_10_publisher_32": {"attribute_name": "\u51fa\u7248\u8005", "attribute_value_mlt": [{"subitem_publisher": "Elsevier"}]}, "item_10_relation_11": {"attribute_name": "DOI", "attribute_value_mlt": [{"subitem_relation_type_id": {"subitem_relation_type_id_text": "https://doi.org/10.1016/j.ejphar.2020.173436", "subitem_relation_type_select": "DOI"}}]}, "item_10_rights_12": {"attribute_name": "\u6a29\u5229", "attribute_value_mlt": [{"subitem_rights": "\u00a9 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/"}]}, "item_10_select_15": {"attribute_name": "\u8457\u8005\u7248\u30d5\u30e9\u30b0", "attribute_value_mlt": [{"subitem_select_item": "author"}]}, "item_10_source_id_61": {"attribute_name": "ISSN\uff08print\uff09", "attribute_value_mlt": [{"subitem_source_identifier": "0014-2999", "subitem_source_identifier_type": "ISSN"}]}, "item_creator": {"attribute_name": "\u8457\u8005", "attribute_type": "creator", "attribute_value_mlt": [{"creatorNames": [{"creatorName": "Hisada, Misaki"}], "nameIdentifiers": [{"nameIdentifier": "103279", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Hiranuma, Minami"}], "nameIdentifiers": [{"nameIdentifier": "103280", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Nakashima, Mio"}], "nameIdentifiers": [{"nameIdentifier": "103281", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Goda, Natsuko"}], "nameIdentifiers": [{"nameIdentifier": "103282", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Tenno, Takeshi"}], "nameIdentifiers": [{"nameIdentifier": "103283", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Hiroaki, Hidekazu"}], "nameIdentifiers": [{"nameIdentifier": "103284", "nameIdentifierScheme": "WEKO"}]}]}, "item_files": {"attribute_name": "\u30d5\u30a1\u30a4\u30eb\u60c5\u5831", "attribute_type": "file", "attribute_value_mlt": [{"accessrole": "open_date", "date": [{"dateType": "Available", "dateValue": "2021-11-15"}], "displaytype": "detail", "download_preview_message": "", "file_order": 0, "filename": "EJP-53411R3-accepted-NUrepository.pdf", "filesize": [{"value": "1.1 MB"}], "format": "application/pdf", "future_date_message": "", "is_thumbnail": false, "licensetype": "license_free", "mimetype": "application/pdf", "size": 1100000.0, "url": {"label": "EJP-53411R3-accepted-NUrepository", "url": "https://nagoya.repo.nii.ac.jp/record/31309/files/EJP-53411R3-accepted-NUrepository.pdf"}, "version_id": "6deda2fc-f51c-4dfa-8f36-556d2f1298dd"}]}, "item_keyword": {"attribute_name": "\u30ad\u30fc\u30ef\u30fc\u30c9", "attribute_value_mlt": [{"subitem_subject": "PDZ domain Inhibitor", "subitem_subject_scheme": "Other"}, {"subitem_subject": "Tight junction", "subitem_subject_scheme": "Other"}, {"subitem_subject": "Zonula occludens-1", "subitem_subject_scheme": "Other"}, {"subitem_subject": "NMR", "subitem_subject_scheme": "Other"}, {"subitem_subject": "Baicalin", "subitem_subject_scheme": "Other"}, {"subitem_subject": "Absorption enhancer", "subitem_subject_scheme": "Other"}, {"subitem_subject": "TGF-\u03b2 signaling pathway", "subitem_subject_scheme": "Other"}, {"subitem_subject": "Epithelial cell barrier", "subitem_subject_scheme": "Other"}]}, "item_language": {"attribute_name": "\u8a00\u8a9e", "attribute_value_mlt": [{"subitem_language": "eng"}]}, "item_resource_type": {"attribute_name": "\u8cc7\u6e90\u30bf\u30a4\u30d7", "attribute_value_mlt": [{"resourcetype": "journal article", "resourceuri": "http://purl.org/coar/resource_type/c_6501"}]}, "item_title": "High dose of baicalin or baicalein can reduce tight junction integrity by partly targeting the first PDZ domain of zonula occludens-1 (ZO-1)", "item_titles": {"attribute_name": "\u30bf\u30a4\u30c8\u30eb", "attribute_value_mlt": [{"subitem_title": "High dose of baicalin or baicalein can reduce tight junction integrity by partly targeting the first PDZ domain of zonula occludens-1 (ZO-1)"}]}, "item_type_id": "10", "owner": "1", "path": ["1903/1904/1905"], "permalink_uri": "http://hdl.handle.net/2237/00033489", "pubdate": {"attribute_name": "\u516c\u958b\u65e5", "attribute_value": "2021-02-08"}, "publish_date": "2021-02-08", "publish_status": "0", "recid": "31309", "relation": {}, "relation_version_is_last": true, "title": ["High dose of baicalin or baicalein can reduce tight junction integrity by partly targeting the first PDZ domain of zonula occludens-1 (ZO-1)"], "weko_shared_id": null}