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The final published version is available at https://doi.org/10.1126/sciimmunol.abl7209.","subitem_rights_language":"en"}]},"item_1617186609386":{"attribute_name":"主題","attribute_value_mlt":[{"subitem_subject":"リポタイコ酸","subitem_subject_language":"ja","subitem_subject_scheme":"Other"},{"subitem_subject":"肝がん","subitem_subject_language":"ja","subitem_subject_scheme":"Other"},{"subitem_subject":"細胞老化随伴分泌現象","subitem_subject_language":"ja","subitem_subject_scheme":"Other"},{"subitem_subject":"肝星細胞","subitem_subject_language":"ja","subitem_subject_scheme":"Other"},{"subitem_subject":"制御性T細胞","subitem_subject_language":"ja","subitem_subject_scheme":"Other"},{"subitem_subject":"SASP因子","subitem_subject_language":"ja","subitem_subject_scheme":"Other"}]},"item_1617186626617":{"attribute_name":"内容記述","attribute_value_mlt":[{"subitem_description":"研究グループは、肝臓に移行した腸内細菌叢の成分であるリポタイコ酸が、肝がん微小環境を変化させてがんの増殖進展を促進するSASP(Senescence-associated secretory phenotype、細胞老化随伴分泌現象)因子を老化肝星細胞から放出させるメカニズムを明らかにしました。がんの組織はがん細胞そのものだけでなく、線維芽細胞や免疫細胞など、様々な種類の細胞種が集まって「がん微小環境」を構成しています。進行したがん組織の微小環境ではがん細胞周囲の細胞ががんの増殖を助長していると考えられています。本グループは、脂肪肝を素地とする肝がん微小環境では、肝星細胞と呼ばれる線維芽細胞が細胞老化を引き起こしており、「細胞老化随伴分泌現象(SASP)」という様々な分泌因子を放出する現象が生じ、その分泌因子(SASP因子)ががんの増殖を促進することを以前から見出していました。しかしこれまでにSASP因子の放出メカニズムについては明らかにされていませんでした。本研究では高脂肪食摂取による肥満誘導性肝がんのマウスモデルを用い、老化肝星細胞の細胞膜上にガスダーミンDというタンパク質が酵素切断されて生じたN末端側の部分(以降GSDMD－Nと略記)が集合して形成される小孔を介して、SASP因子に含まれるサイトカインIL-1βとIL-33が細胞の外部に放出されることを明らかにしました。また、高脂肪食摂取マウスでは、腸管バリアが脆弱化しており、肝臓にグラム陽性腸内細菌の細胞壁成分であるリポタイコ酸が蓄積していました。さらに、蓄積したリポタイコ酸は老化肝星細胞にトル様受容体２(TLR2)を介した刺激を入れ続け、酵素切断で生じたGSDMD－Nによる細胞膜上の小孔形成とそれに続くIL-33やIL-1βの放出を促進していることもわかりました。老化肝星細胞から放出されたIL-33は、その受容体ST2が陽性の制御性T細胞(Treg細胞)に作用し、がんの増殖を促進させることがわかりました。また、GSDMD－NはヒトのNASH(Non-alcoholic steatohepatitis)肝がんの腫瘍部にある肝星細胞でもその存在が認められました。これらの結果から、ガスダーミンDによる小孔形成を阻害する薬剤は肝がんの予防や治療につながる可能性があります。","subitem_description_language":"ja","subitem_description_type":"Abstract"},{"subitem_description":"Long-term senescent cells exhibit a secretome termed the senescence-associated secretory phenotype (SASP). Although the mechanisms of SASP factor induction have been intensively studied, the release mechanism and how SASP factors influence tumorigenesis in the biological context remain unclear. In this study, ...","subitem_description_language":"en","subitem_description_type":"Abstract"},{"subitem_description":"This study was also supported by the Japan Society for the Promotion of Science (JSPS) under grant number 19H04002 (N.O.), 19H03641 (N.K.), 18H02847 (S.N), 21H02963(S.N.), 20K16121 (T.K.), 20K15695 (M.T.), 20K16309 (R.Y.), and Japan Science and Technology agency (JST), the establishment of university fellowships towards the creation of science technology innovation, under grant number JPMJFS 2138 (Y. N), as well as grants from Takeda Science Foundation (N.O. and F. K.) and Yakult Bio-Science Foundation (T.K. and N.O.) and Research Grant of the Princess Takamatsu Cancer Research Fund 18-25003 (N.O.).","subitem_description_language":"en","subitem_description_type":"Other"}]},"item_1617186643794":{"attribute_name":"出版者","attribute_value_mlt":[{"subitem_publisher":"American Association for the Advancement of Science","subitem_publisher_language":"en"}]},"item_1617186783814":{"attribute_name":"識別子","attribute_value_mlt":[{"subitem_identifier_type":"DOI","subitem_identifier_uri":"https://doi.org/10.1126/sciimmunol.abl7209"}]},"item_1617186920753":{"attribute_name":"収録物識別子","attribute_value_mlt":[{"subitem_source_identifier":"2470-9468","subitem_source_identifier_type":"ISSN"}]},"item_1617187056579":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2022-06-24","bibliographicIssueDateType":"Issued"},"bibliographicIssueNumber":"72","bibliographicPageStart":"abl7209","bibliographicVolumeNumber":"7","bibliographic_titles":[{"bibliographic_title":"SCIENCE IMMUNOLOGY","bibliographic_titleLang":"en"}]}]},"item_1617258105262":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"resourcetype":"journal article","resourceuri":"http://purl.org/coar/resource_type/c_6501"}]},"item_1617265215918":{"attribute_name":"出版タイプ","attribute_value_mlt":[{"subitem_version_resource":"http://purl.org/coar/version/c_b1a7d7d4d402bcce","subitem_version_type":"AO"}]},"item_1617353299429":{"attribute_name":"関連情報","attribute_value_mlt":[{"subitem_relation_type":"isVersionOf","subitem_relation_type_id":{"subitem_relation_type_id_text":"https://doi.org/10.1126/sciimmunol.abl7209","subitem_relation_type_select":"DOI"}}]},"item_1722232185104":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2022-07-01"}],"displaytype":"detail","filename":"24709468-7-72-abl7209.pdf","filesize":[{"value":"5.0 MB"}],"format":"application/pdf","mimetype":"application/pdf","url":{"label":"本文","objectType":"fulltext","url":"https://ocu-omu.repo.nii.ac.jp/record/2020472/files/24709468-7-72-abl7209.pdf"},"version_id":"13fb40bc-53b4-4eca-b578-f58b0c98b587"}]},"item_1722577087681":{"attribute_name":"記事種別等","attribute_value_mlt":[{"subitem_description":"RESEARCH ARTICLE","subitem_description_language":"en","subitem_description_type":"Other"}]},"item_1725590125188":{"attribute_name":"言語","attribute_value_mlt":[{"subitem_language":"eng"}]},"item_title":"Gasdermin D-mediated release of IL-33 from senescent hepatic stellate cells promotes obesity-associated hepatocellular carcinoma","item_type_id":"40002","owner":"7","path":["1721355153493"],"pubdate":{"attribute_name":"PubDate","attribute_value":"2022-07-01"},"publish_date":"2022-07-01","publish_status":"0","recid":"2020472","relation_version_is_last":true,"title":["Gasdermin D-mediated release of IL-33 from senescent hepatic stellate cells promotes obesity-associated hepatocellular carcinoma"],"weko_creator_id":"7","weko_shared_id":-1},"updated":"2024-10-31T02:38:31.208138+00:00"}