{"created":"2024-10-29T01:13:36.914795+00:00","id":2006973,"links":{},"metadata":{"_buckets":{"deposit":"270a7997-998a-4cc4-8cbf-eb5dc99fe995"},"_deposit":{"created_by":7,"id":"2006973","owners":[7],"pid":{"revision_id":0,"type":"depid","value":"2006973"},"status":"published"},"_oai":{"id":"oai:tokushima-u.repo.nii.ac.jp:02006973","sets":["1713853213384:1713853296295:1716267876683:1716268551628"]},"author_link":["798","209","427","799","978","1414","10","1548","1542","310"],"item_10001_alternative_title_1":{"attribute_name":"タイトル別表記","attribute_value_mlt":[{"subitem_alternative_title":"ブレオマイシン肺線維症マウスに対するWnt/βカテニン/CBPシグナル新規阻害薬PRI-724の抗線維化効果","subitem_alternative_title_language":"ja"}]},"item_10001_biblio_info_7":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2019-07-12","bibliographicIssueDateType":"Issued"},"bibliographicIssueNumber":"7","bibliographicPageEnd":"199","bibliographicPageStart":"188","bibliographicVolumeNumber":"45","bibliographic_titles":[{"bibliographic_title":"Experimental Lung Research","bibliographic_titleLang":"en"}]}]},"item_10001_description_5":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"Purpose/Aim of the Study: Wnt/β-catenin signaling was reported to be activated in pulmonary fibrosis, and was focused on as a target for antifibrotic therapy. However, the mechanism how the inhibition of Wnt/β-catenin signaling ameliorate pulmonary fibrosis has not been fully elucidated. The purpose of this study is to explore the target cells of Wnt/β-catenin inhibition in pulmonary fibrosis and to examine the antifibrotic effect of the novel inhibitor PRI-724 specifically disrupting the interaction of β-catenin and CBP.\nMaterials and Methods: The effect of C-82, an active metabolite of PRI-724, on the expression of TGF-β1 and α-smooth muscle actin (SMA) was examined on fibroblasts and macrophages. We also examined the effects of PRI-724 in mouse model of bleomycin-induced pulmonary fibrosis.\nResults: The activation and increased accumulation of β-catenin in the canonical pathway were detected in lung fibroblasts as well as macrophages stimulated by Wnt3a using Western blotting. Treatment with C-82 reduced CBP protein and increased p300 protein binding to β-catenin in the nucleus of lung fibroblasts. In addition, C-82 inhibited the expression of SMA in lung fibroblasts treated with TGF-β, indicating the inhibition of myofibroblast differentiation. In the fibrotic lungs induced by bleomycin, β-catenin was stained strongly in macrophages, but the staining of β-catenin in alveolar epithelial cells and fibroblasts was weak. The administration of PRI-724 ameliorated pulmonary fibrosis induced by bleomycin in mice when administered with a late, but not an early, treatment schedule. Analysis of bronchoalveolar fluid (BALF) showed a decreased number of alveolar macrophages. In addition, the level of TGF-β1 in BALF was decreased in mice treated with PRI-724. C-82 also inhibited the production of TGF-β1 by alveolar macrophages.\nConclusions: These results suggest that the β-catenin/CBP inhibitor PRI-724 is a potent antifibrotic agent that acts by modulating the activity of macrophages in the lungs.","subitem_description_language":"en","subitem_description_type":"Abstract"}]},"item_10001_publisher_8":{"attribute_name":"出版者","attribute_value_mlt":[{"subitem_publisher":"Taylor & 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access"}]},"item_1718868208704":{"attribute_name":"備考","attribute_value_mlt":[{"subitem_textarea_language":"ja","subitem_textarea_value":"内容要旨・審査要旨・論文本文の公開\n本論文は，著者Hiroyasu Okazakiの学位論文として提出され，学位審査・授与の対象となっている。\nThis is an Accepted Manuscript of an article published by Taylor & Francis in Experimental Lung Research on 12/07/2019, available online: http://www.tandfonline.com/10.1080/01902148.2019.1638466\n学位授与者所属 : 徳島大学大学院医科学教育部（医学専攻）"}]},"item_1718868303842":{"attribute_name":"学位記番号","attribute_value_mlt":[{"subitem_text_language":"ja","subitem_text_value":"甲医第1431号"}]},"item_1722929371688":{"attribute_name":"出版社版DOI","attribute_value_mlt":[{"subitem_relation_name":[{"subitem_relation_name_language":"ja","subitem_relation_name_text":"10.1080/01902148.2019.1638466"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://doi.org/10.1080/01902148.2019.1638466","subitem_relation_type_select":"DOI"}}]},"item_1723180141928":{"attribute_name":"EID","attribute_value_mlt":[{"subitem_identifier_type":"URI","subitem_identifier_uri":"355461"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"岡﨑, 弘泰","creatorNameLang":"ja"},{"creatorName":"オカザキ, ヒロヤス","creatorNameLang":"ja-Kana"},{"creatorName":"Okazaki, 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