{"created":"2023-05-15T09:41:16.662279+00:00","id":358,"links":{},"metadata":{"_buckets":{"deposit":"ab351a10-00fd-4568-963f-1c38dff903c0"},"_deposit":{"created_by":11,"id":"358","owners":[11],"pid":{"revision_id":0,"type":"depid","value":"358"},"status":"published"},"_oai":{"id":"oai:kagawa-u.repo.nii.ac.jp:00000358","sets":["13:40"]},"author_link":["2930"],"item_10006_date_granted_11":{"attribute_name":"学位授与年月日","attribute_value_mlt":[{"subitem_dategranted":"2019-03-24"}]},"item_10006_degree_grantor_9":{"attribute_name":"学位授与機関","attribute_value_mlt":[{"subitem_degreegrantor":[{"subitem_degreegrantor_language":"ja","subitem_degreegrantor_name":"香川大学"},{"subitem_degreegrantor_language":"en","subitem_degreegrantor_name":"Kagawa University"}],"subitem_degreegrantor_identifier":[{"subitem_degreegrantor_identifier_name":"16201","subitem_degreegrantor_identifier_scheme":"kakenhi"}]}]},"item_10006_degree_name_8":{"attribute_name":"学位名","attribute_value_mlt":[{"subitem_degreename":"博士（医学）","subitem_degreename_language":"ja"}]},"item_10006_description_7":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"Abstract\nActivated coagulation factor XI (FXIa) is a serine proteinase that plays a key role in the intrinsic coagulation pathway. The analysis of FXI-knockout mice has indicated the contribution of FXI to the pathogenesis of atherosclerosis. However, the underlying mechanism remains unknown. We hypothesized that FXIa exerts vascular smooth muscle effects via proteinase-activated receptor 1 (PAR1). Fura-2 fluorometry revealed that FXIa elicited intracellular Ca2+ signal in rat embryo aorta smooth muscle A7r5 cells. The influx of extracellular Ca2+ played a greater role in generating Ca2+ signal than the Ca2+ release from intracellular stores. The FXIa-induced Ca2+ signal was abolished by the pretreatment with atopaxar, an antagonist of PAR1, or 4-amidinophenylmethanesulfonyl fluoride (p-APMSF), an inhibitor of proteinase, while it was also lost in embryonic fibroblasts derived from PAR1−/− mice. FXIa cleaved the recombinant protein containing the extracellular region of PAR1 at the same site (R45/S46) as that of thrombin, a canonical PAR1 agonist. The FXIa-induced Ca2+ influx was inhibited by diltiazem, an L-type Ca2+ channel blocker, and by siRNA targeted to CaV1.2. The FXIa-induced Ca2+ influx was also inhibited by GF109203X and rottlerin, inhibitors of protein kinase C. In a wound healing assay, FXIa increased the rate of cell migration by 2.46-fold of control, which was partly inhibited by atopaxar or diltiazem. In conclusion, FXIa mainly elicits the Ca2+ signal via the PAR1/CaV1.2-mediated Ca2+ influx and accelerates the migration in vascular smooth muscle cells. The present study provides the first evidence that FXIa exerts a direct cellular effect on vascular smooth muscle.","subitem_description_language":"en","subitem_description_type":"Abstract"}]},"item_10006_dissertation_number_12":{"attribute_name":"学位授与番号","attribute_value_mlt":[{"subitem_dissertationnumber":"甲第714号"}]},"item_10006_relation_15":{"attribute_name":"関連サイト","attribute_value_mlt":[{"subitem_relation_type":"isVersionOf","subitem_relation_type_id":{"subitem_relation_type_id_text":"https://doi.org/10.1152/ajpcell.00426.2018","subitem_relation_type_select":"DOI"}},{"subitem_relation_type":"isIdenticalTo","subitem_relation_type_id":{"subitem_relation_type_id_text":"https://dl.ndl.go.jp/pid/11279134","subitem_relation_type_select":"URI"}}]},"item_10006_relation_22":{"attribute_name":"PubMed番号","attribute_value_mlt":[{"subitem_relation_type_id":{"subitem_relation_type_id_text":"30566391","subitem_relation_type_select":"PMID"}}]},"item_10006_relation_28":{"attribute_name":"論文ID（NAID）","attribute_value_mlt":[{"subitem_relation_type_id":{"subitem_relation_type_id_text":"500001345321","subitem_relation_type_select":"NAID"}}]},"item_10006_rights_13":{"attribute_name":"権利","attribute_value_mlt":[{"subitem_rights":"Copyright © 2019 the American Physiological Society","subitem_rights_language":"en"}]},"item_10006_text_30":{"attribute_name":"KEID","attribute_value_mlt":[{"subitem_text_value":"28677"}]},"item_10006_version_type_18":{"attribute_name":"著者版フラグ","attribute_value_mlt":[{"subitem_version_resource":"http://purl.org/coar/version/c_fa2ee174bc00049f","subitem_version_type":"P"}]},"item_access_right":{"attribute_name":"アクセス権","attribute_value_mlt":[{"subitem_access_right":"open access","subitem_access_right_uri":"http://purl.org/coar/access_right/c_abf2"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorAffiliations":[{"affiliationNameIdentifiers":[{"affiliationNameIdentifier":"","affiliationNameIdentifierScheme":"ISNI","affiliationNameIdentifierURI":"http://www.isni.org/isni/"}],"affiliationNames":[{"affiliationName":"","affiliationNameLang":"ja"}]}],"creatorNames":[{"creatorName":"Liu, Wenhua","creatorNameLang":"en"},{"creatorName":"劉, 文華","creatorNameLang":"ja"},{"creatorName":"リュウ, ブンカ","creatorNameLang":"ja-Kana"}],"familyNames":[{"familyName":"Liu","familyNameLang":"en"},{"familyName":"劉","familyNameLang":"ja"},{"familyName":"リュウ","familyNameLang":"ja-Kana"}],"givenNames":[{"givenName":"Wenhua","givenNameLang":"en"},{"givenName":"文華","givenNameLang":"ja"},{"givenName":"ブンカ","givenNameLang":"ja-Kana"}],"nameIdentifiers":[{"nameIdentifier":"2930","nameIdentifierScheme":"WEKO"},{"nameIdentifier":"9000386307869","nameIdentifierScheme":"CiNii ID","nameIdentifierURI":"http://ci.nii.ac.jp/nrid/9000386307869"}]}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2020-11-05"}],"displaytype":"detail","filename":"Med_A714.pdf","filesize":[{"value":"1.3 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kB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"審査の結果の要旨","objectType":"other","url":"https://kagawa-u.repo.nii.ac.jp/record/358/files/Med_A714_result.pdf"},"version_id":"3915bffb-bdda-4b64-8b89-bf2a43de08d6"}]},"item_keyword":{"attribute_name":"キーワード","attribute_value_mlt":[{"subitem_subject":"coagulation factor XI","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"proteinase-activated receptor","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"vascular smooth muscle","subitem_subject_language":"en","subitem_subject_scheme":"Other"}]},"item_language":{"attribute_name":"言語","attribute_value_mlt":[{"subitem_language":"eng"}]},"item_resource_type":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"resourcetype":"doctoral thesis","resourceuri":"http://purl.org/coar/resource_type/c_db06"}]},"item_title":"Coagulation factor XI induces Ca2+ response and accelerates cell migration in vascular smooth muscle cells via proteinase-activated receptor 1","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"Coagulation factor XI induces Ca2+ response and accelerates cell migration in vascular smooth muscle cells via proteinase-activated receptor 1","subitem_title_language":"en"}]},"item_type_id":"10006","owner":"11","path":["40"],"pubdate":{"attribute_name":"PubDate","attribute_value":"2019-04-24"},"publish_date":"2019-04-24","publish_status":"0","recid":"358","relation_version_is_last":true,"title":["Coagulation factor XI induces Ca2+ response and accelerates cell migration in vascular smooth muscle cells via proteinase-activated receptor 1"],"weko_creator_id":"11","weko_shared_id":-1},"updated":"2024-10-31T08:01:23.288999+00:00"}