{"created":"2023-06-20T15:48:49.959489+00:00","id":3360,"links":{},"metadata":{"_buckets":{"deposit":"9180f3e0-9fef-4b7a-adfb-6c260f180a92"},"_deposit":{"created_by":4,"id":"3360","owners":[4],"pid":{"revision_id":0,"type":"depid","value":"3360"},"status":"published"},"_oai":{"id":"oai:hama-med.repo.nii.ac.jp:00003360","sets":["2:15:17"]},"author_link":["9840"],"item_5_alternative_title_1":{"attribute_name":"その他のタイトル","attribute_value_mlt":[{"subitem_alternative_title":"E3リガーゼSkp2の阻害はブレオマイシン誘導性肺線維症を抑制する","subitem_alternative_title_language":"ja"}]},"item_5_biblio_info_5":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2018-02-06","bibliographicIssueDateType":"Issued"},"bibliographicIssueNumber":"2","bibliographicPageStart":"474","bibliographicVolumeNumber":"19","bibliographic_titles":[{"bibliographic_title":"International Journal of Molecular Sciences","bibliographic_titleLang":"en"}]}]},"item_5_date_granted_17":{"attribute_name":"学位授与年月日","attribute_value_mlt":[{"subitem_dategranted":"2018-03-13"}]},"item_5_degree_grantor_15":{"attribute_name":"学位授与機関","attribute_value_mlt":[{"subitem_degreegrantor":[{"subitem_degreegrantor_language":"ja","subitem_degreegrantor_name":"浜松医科大学"}],"subitem_degreegrantor_identifier":[{"subitem_degreegrantor_identifier_name":"13802","subitem_degreegrantor_identifier_scheme":"kakenhi"}]}]},"item_5_degree_name_12":{"attribute_name":"学位名","attribute_value_mlt":[{"subitem_degreename":"博士（医学）","subitem_degreename_language":"ja"}]},"item_5_description_13":{"attribute_name":"学位の区分","attribute_value_mlt":[{"subitem_description":"doctoral","subitem_description_language":"en","subitem_description_type":"Other"}]},"item_5_description_14":{"attribute_name":"学位の分野","attribute_value_mlt":[{"subitem_description":"医学系研究科","subitem_description_language":"ja","subitem_description_type":"Other"}]},"item_5_description_9":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"Idiopathic pulmonary fibrosis (IPF) is a progressive disease with poor prognosis and no curative therapies. SCF-Skp2 E3 ligase is a target for cancer therapy, but there have been no reports about Skp2 as a target for IPF. Here we demonstrate that Skp2 is a promising therapeutic target for IPF. We examined whether disrupting Skp2 suppressed pulmonary fibrosis in a bleomycin (BLM)-induced mouse model and found that pulmonary fibrosis was significantly suppressed in Skp2-deficient mice compared with controls. The pulmonary accumulation of fibrotic markers such as collagen type 1 and fibronectin in BLM-infused mice was decreased in Skp2-deficient mice. Moreover, the number of bronchoalveolar lavage fluid cells accompanied with pulmonary fibrosis was significantly diminished. Levels of the Skp2 target p27 were significantly decreased by BLM-administration in wild-type mice, but recovered in Skp2-/- mice. In vimentin-positive mesenchymal fibroblasts, the decrease of p27-positive cells and increase of Ki67-positive cells by BLM-administration was suppressed by Skp2-deficency. As these results suggested that inhibiting Skp2 might be effective for BLM-induced pulmonary fibrosis, we next performed a treatment experiment using the Skp2 inhibitor SZL-P1-41. As expected, BLM-induced pulmonary fibrosis was significantly inhibited by SZL-P1-41. Moreover, p27 levels were increased by the SZL-P1-41 treatment, suggesting p27 may be an important Skp2 target for BLM-induced pulmonary fibrosis. Our study suggests that Skp2 is a potential molecular target for human pulmonary fibrosis including IPF.","subitem_description_language":"en","subitem_description_type":"Abstract"}]},"item_5_dissertation_number_18":{"attribute_name":"学位授与番号","attribute_value_mlt":[{"subitem_dissertationnumber":"甲第772号"}]},"item_5_publisher_6":{"attribute_name":"出版者","attribute_value_mlt":[{"subitem_publisher":"MDPI","subitem_publisher_language":"en"}]},"item_5_relation_26":{"attribute_name":"PubMed番号","attribute_value_mlt":[{"subitem_relation_type_id":{"subitem_relation_type_id_text":"29415439","subitem_relation_type_select":"PMID"}}]},"item_5_relation_28":{"attribute_name":"出版社DOI","attribute_value_mlt":[{"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://doi.org/10.3390/ijms19020474 ","subitem_relation_type_select":"DOI"}}]},"item_5_source_id_20":{"attribute_name":"EISSN","attribute_value_mlt":[{"subitem_source_identifier":"1422-0067","subitem_source_identifier_type":"EISSN"}]},"item_5_version_type_32":{"attribute_name":"著者版フラグ","attribute_value_mlt":[{"subitem_version_resource":"http://purl.org/coar/version/c_970fb48d4fbd8a85","subitem_version_type":"VoR"}]},"item_access_right":{"attribute_name":"アクセス権","attribute_value_mlt":[{"subitem_access_right":"open access","subitem_access_right_uri":"http://purl.org/coar/access_right/c_abf2"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"美甘, 真史","creatorNameLang":"ja"}],"nameIdentifiers":[{"nameIdentifier":"9840","nameIdentifierScheme":"WEKO"}]}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2019-02-21"}],"displaytype":"detail","filename":"DT_772ronbun.pdf","filesize":[{"value":"6.2 MB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"論文本文","objectType":"fulltext","url":"https://hama-med.repo.nii.ac.jp/record/3360/files/DT_772ronbun.pdf"},"version_id":"ca535fa8-c2c6-4980-8f80-ed78f5d92f8e"}]},"item_keyword":{"attribute_name":"キーワード","attribute_value_mlt":[{"subitem_subject":"Skp2","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"E3 ligase","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"p27","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"bleomycin","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"pulmonary fibrosis","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"mouse model","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"chemical inhibitor","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"idiopathic pulmonary fibrosis (IPF)","subitem_subject_language":"en","subitem_subject_scheme":"Other"}]},"item_language":{"attribute_name":"言語","attribute_value_mlt":[{"subitem_language":"eng"}]},"item_resource_type":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"resourcetype":"doctoral thesis","resourceuri":"http://purl.org/coar/resource_type/c_db06"}]},"item_title":"Inhibiting Skp2 E3 ligase suppresses bleomycin-induced pulmonary fibrosis","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"Inhibiting Skp2 E3 ligase suppresses bleomycin-induced pulmonary fibrosis","subitem_title_language":"en"}]},"item_type_id":"5","owner":"4","path":["17"],"pubdate":{"attribute_name":"PubDate","attribute_value":"2019-02-21"},"publish_date":"2019-02-21","publish_status":"0","recid":"3360","relation_version_is_last":true,"title":["Inhibiting Skp2 E3 ligase suppresses bleomycin-induced pulmonary fibrosis"],"weko_creator_id":"4","weko_shared_id":-1},"updated":"2023-10-17T07:16:15.326734+00:00"}