{"created":"2023-07-27T06:55:03.815393+00:00","id":50721,"links":{},"metadata":{"_buckets":{"deposit":"977ca831-e39c-4c51-bac6-48ea5fdc402b"},"_deposit":{"created_by":18,"id":"50721","owners":[18],"pid":{"revision_id":0,"type":"depid","value":"50721"},"status":"published"},"_oai":{"id":"oai:kanazawa-u.repo.nii.ac.jp:00050721","sets":["2812:2813:2830"]},"author_link":["24839","91837"],"item_9_biblio_info_8":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2004-03","bibliographicIssueDateType":"Issued"},"bibliographicPageStart":"17p.","bibliographicVolumeNumber":"2002-2003","bibliographic_titles":[{"bibliographic_title":"平成15(2003)年度 科学研究費補助金 基盤研究(C) 研究成果報告書"},{"bibliographic_title":"2003 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":"本研究は、糖尿病性血管合併症の発生に重要と考えられている終末糖化産物(AGE, advanced glycation endproducts)とその受容体RAGE(Receptor for AGE)の結合による血管細胞障害のメカニズムについて解明することを目指し、当初計画通りに遂行され、以下の成果を得た。\n1.ウシ血清アルブミンをグリセルアルデヒドまたはグリコールアルデヒドとインキュベートして得られた新規AGE分子種-AGE2とAGE3-が細胞表面RAGEと強く結合することを明らかにした。\n2.表面プラスモン共鳴法を用いた解析により、AGE2・AGE3結合部位は、いずれもRAGEのアミノ端の免疫グロブリンV領域様ドメイン上に存在することを明らかにした。\n3.培養血管内皮細胞を用いた解析により、AGE2・AGE3いずれもERK1・ERK2などのMAPキナーゼ経路を活性化するとともにVCAM-1発現量を増加させることを明らかにした。\n4.RAGEノツクアウト糖尿病マウスでは対照糖尿病マウスに比して糖尿病性腎症の進行が有意に抑制されてることを明らかにし、RAGEが糖尿病性腎症に促進的に働いていることを示した。\n5.ヒト血管内皮細胞から分泌型RAGE蛋白をコードするcDNAを単離し、esRAGE(endogenous secretory RAGE)と命名した。\n6.esRAGEの血管細胞での役割を解析し、esRAGEは細胞外でAGE2・AGE3などのRAGEリガンドを補足することにより、血管保護作用を有することを明らかにした。\n7.esRAGE ELISA定量系を開発し、血中esRAGEと生活習慣病罹患との相関を解析することにより、esRAGEが生活習慣病の罹患リスクマーカーとなる可能性を示した。血中esRAGE量の生活習慣病の罹患リスクマーカーとしての臨床応用に関する特許出願を平成16年5月に予定している。","subitem_description_type":"Abstract"},{"subitem_description":"In this research, we revealed that the novel species of advance glycation endproducts (AGE), whose level in serum is elevated in diabetic patients, do bind to their cellular receptor RAGE and induce intracellular signals.We also identified a novel splicing variant of RAGE-endogenous secretory RAGE (esRAGE)-and found that this variant has protective effect against vascular injury induced by the novel AGE species. Moreover, we found the significant coirelation between serwn esRAGE level and susceptibility of some life-style related diseases.\n(1) We demonstrated that the novel AGE species, which is generated by incubating bovine serum albumin with glyceraldehyde or glycolaldehyde, strongly binds to cellular RAGE at comparable dissociation constants calculated by the suiface plasmon resonance method.\n(2) We mapped the binding region of the novel AGEs on RAGE at an inununoglobulin V-domain-like region on its N-terminal end.\n(3) We demonstrated that the interaction of the new AGEs to RAGE activated MAP kinase signaling pathway and induced V CAM-i expression in cultured human endothelialcells.\n(4) We created RAGE knockout mice and demonstrated that the development of diabetic nephropa thy was dramatically suppressed in the absence of RAGE..\n(5) We isolated a novel splicing variant of RAGE from human endothelial cells that lacks transmembrane domain and is secreted from cells, and termed this novel variant esRAGE (~ndogenous secretory RAGE).\n(6) Furthennore we found that esRAGE has a protective effect against the vascular injuly induced by the novel AGEs, by extracellular capture of the RAGE lingads.\n(7) We established esRAGE ELISA system and analyzed serum level of esRAGE in patients with life-style related deseases. Then we found significant correlation between serum esRAGE level and susceptibility of some life-style related diseases, suggesting that. the serum esRAGE level could be a useful risk marker for some life-style related deseases.","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:14580645, 研究期間(年度):2002-2003","subitem_description_type":"Other"},{"subitem_description":"出典：「新規糖化蛋白分子種による血管障害機序の解明」研究成果報告書　課題番号14580645\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_description_5":{"attribute_name":"提供者所属","attribute_value_mlt":[{"subitem_description":"金沢大学医学系研究科","subitem_description_type":"Other"}]},"item_9_identifier_registration":{"attribute_name":"ID登録","attribute_value_mlt":[{"subitem_identifier_reg_text":"10.24517/00057029","subitem_identifier_reg_type":"JaLC"}]},"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=40303268"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/search/?qm=40303268","subitem_relation_type_select":"URI"}},{"subitem_relation_name":[{"subitem_relation_name_text":"https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-14580645/"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-14580645/","subitem_relation_type_select":"URI"}},{"subitem_relation_name":[{"subitem_relation_name_text":"https://kaken.nii.ac.jp/report/KAKENHI-PROJECT-14580645/145806452003kenkyu_seika_hokoku_gaiyo/"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/report/KAKENHI-PROJECT-14580645/145806452003kenkyu_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":"2021-05-14"}],"displaytype":"detail","filename":"ME-PR-WATANABE-T-kaken 2004-17p.pdf","filesize":[{"value":"564.9 kB"}],"format":"application/pdf","licensetype":"license_11","mimetype":"application/pdf","url":{"label":"ME-PR-WATANABE-T-kaken 2004-17p.pdf","url":"https://kanazawa-u.repo.nii.ac.jp/record/50721/files/ME-PR-WATANABE-T-kaken 2004-17p.pdf"},"version_id":"2a64a31f-9e03-420d-b937-ea44bafed068"}]},"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":"新規糖化蛋白分子種による血管障害機序の解明","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"新規糖化蛋白分子種による血管障害機序の解明"},{"subitem_title":"Study on the mechanism of vascular injury by novel species of advanced glycation endoproducts","subitem_title_language":"en"}]},"item_type_id":"9","owner":"18","path":["2830"],"pubdate":{"attribute_name":"公開日","attribute_value":"2021-05-14"},"publish_date":"2021-05-14","publish_status":"0","recid":"50721","relation_version_is_last":true,"title":["新規糖化蛋白分子種による血管障害機序の解明"],"weko_creator_id":"18","weko_shared_id":-1},"updated":"2023-07-27T14:37:34.638102+00:00"}