{"created":"2023-07-27T06:54:02.918700+00:00","id":49171,"links":{},"metadata":{"_buckets":{"deposit":"a33f7ec5-ff73-41d8-a548-3ead092dbcaf"},"_deposit":{"created_by":18,"id":"49171","owners":[18],"pid":{"revision_id":0,"type":"depid","value":"49171"},"status":"published"},"_oai":{"id":"oai:kanazawa-u.repo.nii.ac.jp:00049171","sets":["2812:2813:2833"]},"author_link":["88087","88086"],"item_9_biblio_info_8":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2001-03","bibliographicIssueDateType":"Issued"},"bibliographicPageStart":"6p.","bibliographicVolumeNumber":"1999-2000","bibliographic_titles":[{"bibliographic_title":"平成12(2000)年度 科学研究費補助金 基盤研究(C) 研究成果報告書"},{"bibliographic_title":"2000 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":"トロンボスポンジン(TSP)タイプIモチーフを有する分泌型のADAMファミリー分子であるADAMTS-1の生理活性および生体における役割について調べている。これまで私は、ADAMTS-1が細胞外マトリックス結合性の活性型メタロプロテアーゼであり、また軟骨プロテオグリカンであるアグリカンのコア蛋白を切断する活性を有することを示してきた。本年度、ADAMTS-1によるアグリカンの切断部位を調べ、ADAMTS-1がアグリカンのコンドロイチン硫酸鎖結合領域のE(1872)-L(1873)部位を切断することを明らかにした。関節炎患者の関節滑液中やインターロイキン1で刺激した軟骨組織培養の上清には、IGDドメイン中のアグリカネース切断部位やコンドロイチン硫酸鎖結合領域のgap領域で切断されたアグリカン断片が検出されることが報告されている。ADAMTS-1切断部位はこれらアグリカンのin vivo切断部位の一つに対応することから、ADAMTS-1がアグリカンのturnoverや関節炎における軟骨組織破壊に関わる可能性が考えられる。また(TSP)タイプIモチーフおよびスペーサー領域からなるADAMTS-1のC末端側領域は硫酸化グリコサミノグリカンに結合する領域であるが、このC末端側領域を欠損させたADAMTS-1の変異体ではアグリカン分解活性が消失することから、ADAMTS-1のC末端側領域とアグリカンの糖鎖との結合がその分解活性に必要であると考えられる。一方、ADAMTS-1遺伝子欠損マウスでは、腎臓における腎杯の拡張に加え、副腎髄質組織の構造が異常で多くの空洞状の構造が認められた。またADAMTS-1遺伝子欠損の雌マウスは強い不妊傾向を示すことから、ADAMTS-1は副腎髄質組織の構築や女性生殖器の機能にも必須に関わることが示唆された。","subitem_description_type":"Abstract"},{"subitem_description":"ADAMTS-1 is an ADAM family protein with thrombospondin (TSP) type I motifs. We previously established that ADAMTS-1 is an extracellular matrix-anchored metalloproteinase. In this study, we found that ADAMTS-1 is able to cleave a major cartilage proteoglycan, aggrecan. N-terminal sequencing analysis of the cleavage product revealed that ADAMTS-1 cleaves the Glu^<1871>-Leu^<1872> bond within the chondroitin sulfate attachment domain of aggrecan. In addition to two proteolytic cleavage sites within the IGD, proteolysis of aggrecan within the CS attachment domain has been reported in cartilage explant cultures and in the synovial fluid of arthritis patients. Since the ADAMTS-1 cleavage site corresponds to one of these in vivo cleavage sites of aggrecan, it is possible that ADAMTS-1 be involved in the turnover of aggrecan in vivo. In addition, deletional analysis demonstrated that the C-terminal spacer region of ADAMTS-1 is necessary for the degradation of aggrecan.\nTo identify the physiological role of ADAMTS-1, we disrupted the mouse ADAMTS-1 gene. We found that ADAMTS-1 gene knockout mice show enlargement of the calyx, which resembles ureteropelvic junction obstruction in human. In addition to renal anomalies, an abnormal adrenal medullary architecture was observed in ADAMTS-1 (-/-) mice. Moreover, fertilization was impaired in ADAMTS-1 (-/-) females. These findings demonstrate that ADAMTS-1 is a multifunctional metalloproteinase that is necessary for the stucture and function of the ureteropelvic junction and adrenal glands as well as of the female genital organs.","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:11670316, 研究期間(年度):1999-2000","subitem_description_type":"Other"},{"subitem_description":"出典：「炎症時に発見されるADAMTS-1プロテアーゼに関する基質の検索」研究成果報告書　課題番号11670316\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":"10.24517/00055484","subitem_identifier_reg_type":"JaLC"}]},"item_9_publisher_17":{"attribute_name":"公開者","attribute_value_mlt":[{"subitem_publisher":"金沢大学がん進展制御研究所"}]},"item_9_relation_28":{"attribute_name":"関連URI","attribute_value_mlt":[{"subitem_relation_name":[{"subitem_relation_name_text":"https://kaken.nii.ac.jp/search/?qm=40242565"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/search/?qm=40242565","subitem_relation_type_select":"URI"}},{"subitem_relation_name":[{"subitem_relation_name_text":"https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11670316/"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11670316/","subitem_relation_type_select":"URI"}},{"subitem_relation_name":[{"subitem_relation_name_text":"https://kaken.nii.ac.jp/report/KAKENHI-PROJECT-11670316/116703162000kenkyu_seika_hokoku_gaiyo/"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/report/KAKENHI-PROJECT-11670316/116703162000kenkyu_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":"2019-09-27"}],"displaytype":"detail","filename":"CA-PR-KUNO-K-kaken 2001-6p.pdf","filesize":[{"value":"1.3 MB"}],"format":"application/pdf","licensetype":"license_11","mimetype":"application/pdf","url":{"label":" CA-PR-KUNO-K-kaken 2001-6p.pdf","url":"https://kanazawa-u.repo.nii.ac.jp/record/49171/files/CA-PR-KUNO-K-kaken 2001-6p.pdf"},"version_id":"f450d41e-ebc7-4d58-9722-ee4fb40bfdf0"}]},"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":"炎症時に発見されるADAMTS-1プロテアーゼに関する基質の検索","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"炎症時に発見されるADAMTS-1プロテアーゼに関する基質の検索"},{"subitem_title":"Analysis of substrates for ADAMTS-1 metalloproteinase","subitem_title_language":"en"}]},"item_type_id":"9","owner":"18","path":["2833"],"pubdate":{"attribute_name":"公開日","attribute_value":"2019-09-27"},"publish_date":"2019-09-27","publish_status":"0","recid":"49171","relation_version_is_last":true,"title":["炎症時に発見されるADAMTS-1プロテアーゼに関する基質の検索"],"weko_creator_id":"18","weko_shared_id":-1},"updated":"2023-07-27T14:46:41.179147+00:00"}