{"created":"2023-07-27T06:51:06.421988+00:00","id":44378,"links":{},"metadata":{"_buckets":{"deposit":"b6ba0654-e6e3-4c84-bed5-33be774990c6"},"_deposit":{"created_by":18,"id":"44378","owners":[18],"pid":{"revision_id":0,"type":"depid","value":"44378"},"status":"published"},"_oai":{"id":"oai:kanazawa-u.repo.nii.ac.jp:00044378","sets":["2812:2813:2829"]},"author_link":["23919","55"],"item_9_biblio_info_8":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2005-03","bibliographicIssueDateType":"Issued"},"bibliographicPageStart":"9p.","bibliographicVolumeNumber":"2003-2004","bibliographic_titles":[{"bibliographic_title":"平成16(204)年度 科学研究費補助金 基盤研究(B) 研究成果報告書"},{"bibliographic_title":"2004 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":"スフィンゴシン-1-リン酸(S1P)-Edgシステムの病態生理的意義の解明を目的として以下のインビトロ及びインビボでの成果を得た。S1P-Edgシステムによる二方向性細胞運動制御の分子機序を検討し、Edg1とEdg3はGiを介してRacを活性化し細胞運動を促進するのに対し、Edg5はG12/13、Rhoを介してRacを制御し細胞運動をすることを見い出した。S1Pは傷害血管新生内膜細胞における血管平滑筋増殖因子PDGF産生を促進した。この作用は、Edg1(=S1P_1)受容体を介し、Gi-Ras-ERK/p38MAPKからなる情報伝達経路に依存した。さらに、ERK/p38MAPKは血管平滑筋形質転換に重要な役割を果たす転写因子KLF5を誘導し、PDGF遺伝子の転写を活性化することを見出した。この他に、Edg5(=S1P_2)及びEdg3(=S1P_3)を介したRho-Rhoキナーゼ経路の活性化もPDGF発現に寄与した。Edg5は血管平滑筋細胞において強力にRhoを活性化し細胞運動を抑制することを見出していたが、Edg5によるRho活性化が一般に知られている三量体G蛋白G_<12/13>の他にG_qを介することを見出した。S1Pが血管内皮細胞に発現しているEdg1、Edg3を介して細胞遊走、細胞増殖を促進し血管新生を誘導することが示されているが、少なくとも一部の内皮細胞にはEdg5も発現しており、Edg5はEdg1、Edg3とは逆に細胞遊走を抑制して血管新生の抑制を引き起こすことを見出した。Edg1トランスジェニック(TG)マウス、S1P合成酵素スフィンゴシンキナーゼ(SK)TGマウスなどを用いて、個体レベルでのS1P-Edgシステムの血管新生、血管リモデリングなどに及ぼす作用を検討した。Edg1作用の増強、S1P合成の亢進は心血管ホメオスターシスに影響し、心血管の生理機能に変化をもたらすこと、また病態生理において役割を担うことが示唆された。","subitem_description_type":"Abstract"},{"subitem_description":"In order to delineate physiological and pathophysiological roles of sphingosine-1-phosphate (S1P), we conducted the following in vitro and in vivo investigations. S1P and its receptors regulate cell motility both positively and negatively. The S1P receptors Edg1 and Edg3 mediate Rac stimulation and thereby chemotaxis via Gi, whereas Edg5 mediates Rac inhibition and cell migration inhibition via G12/13 and Rho. Available evidence suggests that S1P could affect vascular smooth muscle accumulation in injured blood vessels. We found that S1P stimulated mRNA expression of platelet-derived growth factor (PDGF) A and B chains in neointimal smooth muscle. This stimulatory effect was mediated via Edg1-Gi-Ras-ERK/p38MAPK and Edg3/Edg5-Rho-Rho kinase. The ERK and p38MAPK mediated stimulation of KLF5 expression, which was necessary and sufficient for PDGF gene expression. S1P inhibits migration of vascular smooth muscle cells. This action was accompanied by Rac inhibition. Interestingly, both G12/13 and Gq were involved in S1P-induced Rac inhibition in vascular smooth muscle cells. In addition to Edg1 and Edg3, vascular endothelial cells express Edg5, which mediates inhibition of endothelial cell migration and capillary like tube formation. We generated Edg1-transgenic and sphingosine kinase-transgenic mice, and analyzed their phenotypes. Preliminary results show that S1P-Edg system is involved in the homeostasis of the cardiovascular system.","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:15390063, 研究期間(年度):2003-2004","subitem_description_type":"Other"},{"subitem_description":"出典：「生理活性脂質スフィンゴシン-1-リン酸・Edg受容体システムの分子生理学的研究」研究成果報告書　課題番号15390063\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":"10.24517/00050720","subitem_identifier_reg_type":"JaLC"}]},"item_9_publisher_17":{"attribute_name":"公開者","attribute_value_mlt":[{"subitem_publisher":"金沢大学医薬保健研究域医学系"}]},"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=60171592"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/search/?qm=60171592","subitem_relation_type_select":"URI"}},{"subitem_relation_name":[{"subitem_relation_name_text":"https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-15390063/"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-15390063/","subitem_relation_type_select":"URI"}},{"subitem_relation_name":[{"subitem_relation_name_text":"https://kaken.nii.ac.jp/report/KAKENHI-PROJECT-15390063/153900632004kenkyu_seika_hokoku_gaiyo/"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/report/KAKENHI-PROJECT-15390063/153900632004kenkyu_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":"2018-05-14"}],"displaytype":"detail","filename":"ME-PR-TAKUWA-Y-kaken 2005-9p.pdf","filesize":[{"value":"405.7 kB"}],"format":"application/pdf","licensetype":"license_11","mimetype":"application/pdf","url":{"label":"ME-PR-TAKUWA-Y-kaken 2005-9p.pdf","url":"https://kanazawa-u.repo.nii.ac.jp/record/44378/files/ME-PR-TAKUWA-Y-kaken 2005-9p.pdf"},"version_id":"0f19746c-1336-4b37-b278-69748d3250d2"}]},"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":"生理活性脂質スフィンゴシン-1-リン酸・Edg受容体システムの分子生理学的研究","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"生理活性脂質スフィンゴシン-1-リン酸・Edg受容体システムの分子生理学的研究"},{"subitem_title":"Molecular dissection of the physiological role of bioactive sphingosine-1-phosphate and Edg receptors","subitem_title_language":"en"}]},"item_type_id":"9","owner":"18","path":["2829"],"pubdate":{"attribute_name":"公開日","attribute_value":"2018-05-14"},"publish_date":"2018-05-14","publish_status":"0","recid":"44378","relation_version_is_last":true,"title":["生理活性脂質スフィンゴシン-1-リン酸・Edg受容体システムの分子生理学的研究"],"weko_creator_id":"18","weko_shared_id":-1},"updated":"2023-07-27T14:29:06.350709+00:00"}