{"created":"2023-05-15T09:47:38.426517+00:00","id":9802,"links":{},"metadata":{"_buckets":{"deposit":"59733576-278c-42df-b98a-a1c048651940"},"_deposit":{"created_by":11,"id":"9802","owners":[11],"pid":{"revision_id":0,"type":"depid","value":"9802"},"status":"published"},"_oai":{"id":"oai:kagawa-u.repo.nii.ac.jp:00009802","sets":["13:40"]},"author_link":["3709"],"item_10006_alternative_title_1":{"attribute_name":"その他（別言語等）のタイトル","attribute_value_mlt":[{"subitem_alternative_title":"エストラジオールの主要な代謝産物である2‐メトキシストラジオールはHepG2細胞において肝ABCA1の発現を増加させる","subitem_alternative_title_language":"ja"}]},"item_10006_date_granted_11":{"attribute_name":"学位授与年月日","attribute_value_mlt":[{"subitem_dategranted":"2022-06-29"}]},"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":"ATP-binding cassette transporter A1 (ABCA1) is a key regulator of lipid efflux, and the absence of ABCA1 induces hepatic lipid accumulation, which is one of the major causes of fatty liver. 2-Methoxyestradiol (2-ME2) has been demonstrated to protect against fatty liver. In this study, we investigated the effects of 2-ME2 on the hepatic lipid content and ABCA1 expression. We found that 2-ME2 dose-dependently increased ABCA1 expression, and therefore, the lipid content was significantly decreased in HepG2 cells. 2-ME2 enhanced the ABCA1 promoter activity; however, this effect was reduced after the inhibition of the PI3K pathway. The overexpression of Akt or p110 induced ABCA1 promoter activity, while dominant-negative Akt diminished the ability of 2-ME2 on ABCA1 promoter activity. Further, 2-ME2 stimulated the rapid phosphorylation of Akt and FoxO1 and reduced the nuclear accumulation of FoxO1. Chromatin immunoprecipitation confirmed that FoxO1 bonded to the ABCA1 promoter region. The binding was reduced by 2-ME2, which facilitated ABCA1 gene transcription. Furthermore, mutating FoxO1-binding sites in the ABCA1 promoter region or treatment with FoxO1-specific siRNA disrupted the effect of 2-ME2 on ABCA1 expression. All of our results demonstrated that 2-ME2 might upregulate ABCA1 expression via the PI3K/Akt/FoxO1 pathway, which thus reduces the lipid content in hepatocytes.","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814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/10.3390/nu14020288","subitem_relation_type_select":"DOI"}},{"subitem_relation_type":"hasVersion","subitem_relation_type_id":{"subitem_relation_type_id_text":"http://www.ncbi.nlm.nih.gov/pmc/articles/pmc8779252/","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":"35057469","subitem_relation_type_select":"PMID"}}]},"item_10006_rights_13":{"attribute_name":"権利","attribute_value_mlt":[{"subitem_rights":"© 2022 by the authors. Licensee MDPI, Basel, Switzerland.","subitem_rights_language":"en"},{"subitem_rights":"This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).","subitem_rights_language":"en"}]},"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":[{"creatorNames":[{"creatorName":"井端, 智裕","creatorNameLang":"ja"},{"creatorName":"イバタ, トモヒロ","creatorNameLang":"ja-Kana"},{"creatorName":"Ibata, Tomohiro","creatorNameLang":"en"}],"nameIdentifiers":[{},{},{}]}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2022-07-07"}],"displaytype":"detail","filename":"Med_A814.pdf","filesize":[{"value":"609.3 kB"}],"format":"application/pdf","licensetype":"license_6","mimetype":"application/pdf","url":{"label":"本文","objectType":"fulltext","url":"https://kagawa-u.repo.nii.ac.jp/record/9802/files/Med_A814.pdf"},"version_id":"8e90763d-a4db-4999-8cbb-5bf5e54d9bf5"},{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2022-07-07"}],"displaytype":"detail","filename":"Med_A814_abstract.pdf","filesize":[{"value":"90.8 kB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"内容の要旨","objectType":"abstract","url":"https://kagawa-u.repo.nii.ac.jp/record/9802/files/Med_A814_abstract.pdf"},"version_id":"89bc8b7e-808a-418f-aa9b-1e3f45c3e90e"},{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2022-07-07"}],"displaytype":"detail","filename":"Med_A814_result.pdf","filesize":[{"value":"85.9 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/9802/files/Med_A814_result.pdf"},"version_id":"3abfbfef-2ca1-41cf-a8b2-f272d686a46f"}]},"item_keyword":{"attribute_name":"キーワード","attribute_value_mlt":[{"subitem_subject":"ABCA1","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"2-methoxyestradiol","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"lipid accumulation","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"fatty liver","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"cell signaling","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":"Effects of 2‐methoxyestradiol, a main metabolite of estradiol on Hepatic ABCA1 expression in HepG2 cells","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"Effects of 2‐methoxyestradiol, a main metabolite of estradiol on Hepatic ABCA1 expression in HepG2 cells","subitem_title_language":"en"}]},"item_type_id":"10006","owner":"11","path":["40"],"pubdate":{"attribute_name":"PubDate","attribute_value":"2022-07-07"},"publish_date":"2022-07-07","publish_status":"0","recid":"9802","relation_version_is_last":true,"title":["Effects of 2‐methoxyestradiol, a main metabolite of estradiol on Hepatic ABCA1 expression in HepG2 cells"],"weko_creator_id":"11","weko_shared_id":-1},"updated":"2023-10-16T02:32:22.598028+00:00"}