{"created":"2023-07-27T06:58:25.620769+00:00","id":56763,"links":{},"metadata":{"_buckets":{"deposit":"84064f75-82b6-4396-a726-4b049c1a399d"},"_deposit":{"created_by":18,"id":"56763","owners":[18],"pid":{"revision_id":0,"type":"depid","value":"56763"},"status":"published"},"_oai":{"id":"oai:kanazawa-u.repo.nii.ac.jp:00056763","sets":["2812:2813:2827"]},"author_link":["99369","20132"],"item_9_biblio_info_8":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2008-05-26","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(C) 研究成果報告書概要"},{"bibliographic_title":"2006 Fiscal Year Final Research Report Summary","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":"本研究の目的は、可溶型糖化蛋白受容体(receptor for AGE, RAGE)mRNAと可溶型VEGF受容体(Flt-1)mRNAを生成する選択的mRNAスプライシング/プロセシングの医学・生物学的意義を明らかにするとともに、その制御機構を解明して、血管新生や糖尿病血管合併症などの血管障害が関与する疾患のリスク予知・予防・治療法開発に向けた新規原理を打ち立てることである。平成17〜18年度の研究で以下の成果を得た。\n(i)可溶型RAGEmRNA選択的スプライシング\n(1)RT-PCRクローニングによりヒト可溶型RAGEに相当するマウスcDNAを分離した。\n(2)免疫組織化学法により、可溶型RAGEは血管、神経、膵β細胞、単球、胆管、顎下腺などを含む多くのヒト組織で発現していることを明らかにした。\n(3)ELISAを開発し、血液中の可溶型RAGE濃度と動脈硬化との関連を検討したところ、血中可溶型RAGE濃度は動脈硬化の進行と逆相関を示した。\n(4)ヒトRAGEミニ遺伝子とヒト由来HEK293T細胞を用いたRAGEmRNA選択的スプライシング解析系を確立し、各種ミニ遺伝子変異体を用いた解析により、可溶型RAGEmRNA産生を制御する配列を同定した。\n(5)hnRNP-Hが可溶型RAGEmRNA産生に促進的に作用することを明らかにした。\n(ii)VEGF受容体(Flt-1)mRNAの選択的3'端プロセシング\n(1)ヒト血管内皮細胞で産生されるFlt-1mRNAの3'端プロセシング/ポリA付加部位を3'-RACE法により決定した。\n(2)ヒトFlt-1のミニ遺伝子とヒト初代培養血管内皮細胞を用いたFlt-1mRNA選択的3'端プロセシング解析系を確立し、site-directed mutagenesisにより可溶型Flt-1mRNAの産生に必須な配列とそこに作用すると考えられる因子を同定した。","subitem_description_type":"Abstract"},{"subitem_description":"In this research, we studied the mechanisms of alternative pre-mRNA splicing/processing by which mRNAs for soluble RAGE and soluble VEGF receptor are produced, and their roles in the regulation of diabetic vascular complications and angiogenesis. Soluble RAGE has a protective activity against AGE-induced vascular cell injury and soluble VEGF receptor acts as a potent anti-angiogenic factor.\n(1) We isolated the marine equivalent of soluble RAGE by RT-PCR cloning. This study will provide an animal orthologue of soluble RAGE to clarify its roles in health and disease.\n(2) We investigated the expression of soluble RAGE protein in human organs and tissues by immunohistochemical analysis, and found that soluble RAGE was widely distributed in various organs and tissues including vascular endothelium, neurons, pancreatic β cells, macrophages/monocytes, bile ducts, salivary glands, digestive tracts, renal tubules, prostate, skin, and thyroid.\n(3) We developed enzyme-linked immunosorbent assay (ELISA) for human soluble RAGE and examined the association of plasma soluble RAGE level with atherosclerosis, and found that it inversely correlated with carotid or femoral atherosclerosis.\n(4) We established an assay system for RAGE alternative splicing using a human RAGE mini-gene and HEK293T cells. Transfection experiments with various mutant RAGE mini-genes identified cis-acting elements on RAGE pre-mRNA, which regulated the alternative splicing of soluble RAGE mRNA. We also found the involvement of hnRNP-H in the regulation of soluble RAGE mRNA production.\n(4) We established an assay system for alternative 3'-end processing of VEGF receptor-1 (Flt-1) mRNA using a human Flt-1 mini-gene and primary cultured human vascular endothelial cells, and identified a cis-acting element on Flt-1 pre-mRNA, which regulated the production of soluble Flt-1 mRNA.","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:17590241, 研究期間(年度):2005 – 2006","subitem_description_type":"Other"},{"subitem_description":"出典：「血管新生・糖尿病血管症罹患感受性を制御する選択的mRNAスプライシングの新機構」研究成果報告書　課題番号17590241\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（https://kaken.nii.ac.jp/ja/report/KAKENHI-PROJECT-17590241/175902412006kenkyu_seika_hokoku_gaiyo/)を加工して作成","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":"10.24517/00063037","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://nrid.nii.ac.jp/ja/search/?kw=80240373"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://nrid.nii.ac.jp/ja/search/?kw=80240373","subitem_relation_type_select":"URI"}},{"subitem_relation_name":[{"subitem_relation_name_text":"https://kaken.nii.ac.jp/ja/grant/KAKENHI-PROJECT-17590241/"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/ja/grant/KAKENHI-PROJECT-17590241/","subitem_relation_type_select":"URI"}},{"subitem_relation_name":[{"subitem_relation_name_text":"https://kaken.nii.ac.jp/ja/report/KAKENHI-PROJECT-17590241/175902412006kenkyu_seika_hokoku_gaiyo/"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/ja/report/KAKENHI-PROJECT-17590241/175902412006kenkyu_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":"2021-10-29"}],"displaytype":"detail","filename":"ME-PR-YONEKURA-H-kaken 2008-4p.pdf","filesize":[{"value":"183.3 kB"}],"format":"application/pdf","licensetype":"license_11","mimetype":"application/pdf","url":{"label":"ME-PR-YONEKURA-H-kaken 2008-4p.pdf","url":"https://kanazawa-u.repo.nii.ac.jp/record/56763/files/ME-PR-YONEKURA-H-kaken 2008-4p.pdf"},"version_id":"aeac0586-84ff-47a1-baa4-444a2522d211"}]},"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":"血管新生・糖尿病血管症罹患感受性を制御する選択的mRNAスプライシングの新機構","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"血管新生・糖尿病血管症罹患感受性を制御する選択的mRNAスプライシングの新機構"},{"subitem_title":"Study on the mechanisms of alternative mRNA splicing that regulates the regulation of angiogenesis and diabetic complication susceptibility","subitem_title_language":"en"}]},"item_type_id":"9","owner":"18","path":["2827"],"pubdate":{"attribute_name":"公開日","attribute_value":"2021-10-29"},"publish_date":"2021-10-29","publish_status":"0","recid":"56763","relation_version_is_last":true,"title":["血管新生・糖尿病血管症罹患感受性を制御する選択的mRNAスプライシングの新機構"],"weko_creator_id":"18","weko_shared_id":-1},"updated":"2023-07-27T14:32:37.182237+00:00"}