{"created":"2023-07-27T06:44:30.057103+00:00","id":34747,"links":{},"metadata":{"_buckets":{"deposit":"efc93c30-f6bb-458e-b7f1-2de654fc04c6"},"_deposit":{"created_by":3,"id":"34747","owners":[3],"pid":{"revision_id":0,"type":"depid","value":"34747"},"status":"published"},"_oai":{"id":"oai:kanazawa-u.repo.nii.ac.jp:00034747","sets":["2812:2813:2827"]},"author_link":["23232","9956"],"item_9_biblio_info_8":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2007-05-01","bibliographicIssueDateType":"Issued"},"bibliographicPageStart":"4p.","bibliographicVolumeNumber":"2005-2006","bibliographic_titles":[{"bibliographic_title":"平成18(2006)年度 科学研究費補助金 基盤研究(B) 研究成果報告書"},{"bibliographic_title":"2006 Fiscal Year Final Research Report","bibliographic_titleLang":"en"}]}]},"item_9_creator_33":{"attribute_name":"著者別表示","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{}],"nameIdentifiers":[{},{}]}]},"item_9_description_21":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"膜型マトリックスメタロプロテアーゼー1(MT1-MMP)はがん、炎症性疾患などに密接に関与している。これら疾患におけるMT1-MMPの機能を明らかにする目的で発現クローニング法を開発し、新規基質の探索を行い以下の分子を同定した。 1.アポリポプロテインE(ApoE)は脂質代謝の制御以外にも血管平滑筋の細胞増殖や細胞運動を阻害する。MT1-MMPはApoEを切断・不活化することを見出した。リコンビナントApoEはHEK293T細胞の増殖を抑制したが、MT1-MMPによる分解はApoEによる細胞増殖抑制活性を喪失させた。MT1-MMPによるapoEの分解は、apoEによって阻害されていた血管平滑筋の細胞増殖や細胞運動能を回復させ、創傷治癒の重要なステップである組織再構築の促進に貢献することが示唆された。 2.アミロイド前駆体タンパク(APP)はMT-MMPファミリーの内、MT1-MMP以外にも脳で特異的に発現するMT3-MMP,MT5-MMPによりベーターペプチド配列内で切断・シェディングされた。しかし、MT1-MMPはアルファーセクレターゼにもかかわらずベーターアミロイドの産生は低下しなかったことから、ベーターアミロイドペプチドの産生は細胞表面で起こるのではないことが強く示唆された。 3.MT1-MMPはTGFベーターファミリーのGDF15/MIC-1のmature formのAsn252-Met253間を切断し、サイトカイン活性を失活させた。GDF15はがん細胞に作用し、p53活性化(リン酸化)、p21の産生を促進することにより増殖を阻害するがMT1-MMPによる切断により増殖抑制活性を喪失した。よってGDF15とMMP阻害剤の併用ががん細胞の増殖抑制には効果的であった。","subitem_description_type":"Abstract"},{"subitem_description":"Membrane-type matrix metalloproteinase-1 (MT1-MMP) is closely associated with tumor, inflammatory diseases and so on. To explore the function of MT1-MMP in these diseases, we developed expression cloning strategy to identify novel substrates for it, and identified following substrates.\n1. Apolipoprotein E (ApoE) is involved in not only lipoprotein clearance but also cell regulatory functions that prevent vascular disease. We identified ApoE as a substrate for MT1-MMP. Cleavage of ApoE by MT1-MMP may abrogate suppression of growth and migration of smooth muscle cells by ApoE, and contribute to the stimulation of tissue remodeling.\n2. Amyloid precursor protein (APP) was shown to be cleaved by MT1-MMP and brain-specific MT3-MMP and MT5-MMP within a beta peptide sequence, and the cytoplasmid domain was shed into culture medium. Although these MT-MMPs are alpha secretases, synthesis of beta amyloid peptide was not reduced by them. These results suggest that beta amyloid peptide may not be generated on cell surface.\n3. MT1-MMP was shown to cleave the mature form of a TGF beta family member GDF15/MIC-1 at Asn252-Met253 peptide bond and inactivate cytokine activity. GDF15 suppressed tumor cell growth by inducing phosphorylation of p53 and synthesis of p21. Thus, cleavage of GDF15 by MT1-MMP abrogated growth suppression of tumor cells. These results suggested that combination therapy of GDF15 and MMP inhibitor may have potent growth inhibitory effect on tumor cells.","subitem_description_type":"Abstract"}]},"item_9_description_22":{"attribute_name":"内容記述","attribute_value_mlt":[{"subitem_description":"研究課題/領域番号:17390090, 研究期間(年度):2005–2006","subitem_description_type":"Other"},{"subitem_description":"出典：「組織破壊に関わるマトリックスメタロプロテアーゼの機能解析」研究成果報告書　課題番号17390090\n  (KAKEN：科学研究費助成事業データベース（国立情報学研究所）)\n　　　本文データは著者版報告書より作成","subitem_description_type":"Other"}]},"item_9_identifier_registration":{"attribute_name":"ID登録","attribute_value_mlt":[{"subitem_identifier_reg_text":"10.24517/00034734","subitem_identifier_reg_type":"JaLC"}]},"item_9_publisher_17":{"attribute_name":"公開者","attribute_value_mlt":[{"subitem_publisher":"金沢大学がん研究所"}]},"item_9_relation_28":{"attribute_name":"関連URI","attribute_value_mlt":[{"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/search/?qm=00115239","subitem_relation_type_select":"URI"}},{"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-17390090/","subitem_relation_type_select":"URI"}},{"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/report/KAKENHI-PROJECT-17390090/173900902006kenkyu_seika_hokoku_gaiyo/","subitem_relation_type_select":"URI"}}]},"item_9_version_type_25":{"attribute_name":"著者版フラグ","attribute_value_mlt":[{"subitem_version_resource":"http://purl.org/coar/version/c_ab4af688f83e57aa","subitem_version_type":"AM"}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2017-10-05"}],"displaytype":"detail","filename":"CA-PR-SATO-H-kaken 2007-4p.pdf","filesize":[{"value":"166.2 kB"}],"format":"application/pdf","licensetype":"license_11","mimetype":"application/pdf","url":{"label":"CA-PR-SATO-H-kaken 2007-4p.pdf","url":"https://kanazawa-u.repo.nii.ac.jp/record/34747/files/CA-PR-SATO-H-kaken 2007-4p.pdf"},"version_id":"eec278a4-2853-42d9-a7af-07f37ad98c9d"}]},"item_language":{"attribute_name":"言語","attribute_value_mlt":[{"subitem_language":"jpn"}]},"item_resource_type":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"resourcetype":"research report","resourceuri":"http://purl.org/coar/resource_type/c_18ws"}]},"item_title":"組織破壊に関わるマトリックスメタロプロテアーゼの機能解析","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"組織破壊に関わるマトリックスメタロプロテアーゼの機能解析"},{"subitem_title":"Functional analysis of matrix metalloproteinases associated with tissue destruction","subitem_title_language":"en"}]},"item_type_id":"9","owner":"3","path":["2827"],"pubdate":{"attribute_name":"公開日","attribute_value":"2017-10-05"},"publish_date":"2017-10-05","publish_status":"0","recid":"34747","relation_version_is_last":true,"title":["組織破壊に関わるマトリックスメタロプロテアーゼの機能解析"],"weko_creator_id":"3","weko_shared_id":3},"updated":"2023-07-27T14:34:47.803542+00:00"}