{"created":"2023-06-19T10:29:09.099015+00:00","id":1264,"links":{},"metadata":{"_buckets":{"deposit":"fd2ac547-e52c-473a-831b-e3dc39db2a2f"},"_deposit":{"created_by":31,"id":"1264","owners":[31],"pid":{"revision_id":0,"type":"depid","value":"1264"},"status":"published"},"_oai":{"id":"oai:kwmed.repo.nii.ac.jp:00001264","sets":["1709617079800:35:262:505"]},"author_link":["114295","114296"],"item_1694495855422":{"attribute_name":"著者版フラグ","attribute_value_mlt":[{"subitem_version_type":"VoR"}]},"item_3_biblio_info_12":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2002","bibliographicIssueDateType":"Issued"},"bibliographicIssueNumber":"3","bibliographicPageEnd":"174","bibliographicPageStart":"165","bibliographicVolumeNumber":"28","bibliographic_titles":[{"bibliographic_title":"川崎医学会誌","bibliographic_titleLang":"ja"},{"bibliographic_title":"Kawasaki medical journal","bibliographic_titleLang":"en"}]}]},"item_3_description_8":{"attribute_name":"記事種別(日)","attribute_value_mlt":[{"subitem_description":"原著","subitem_description_language":"ja","subitem_description_type":"Other"}]},"item_3_identifier_14":{"attribute_name":"URL","attribute_value_mlt":[{"subitem_identifier_type":"URI","subitem_identifier_uri":"http://igakkai.kms-igakkai.com/wp/wp-content/uploads/2002/KMJ28(3)165-174.2002.pdf"}]},"item_3_relation_20":{"attribute_name":"DOI","attribute_value_mlt":[{"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://doi.org/10.11482/KMJ28(3)165-174.2002.pdf","subitem_relation_type_select":"DOI"}}]},"item_3_source_id_1":{"attribute_name":"雑誌書誌ID","attribute_value_mlt":[{"subitem_source_identifier":"AN00045593","subitem_source_identifier_type":"NCID"},{"subitem_source_identifier":"AN12940574","subitem_source_identifier_type":"NCID"}]},"item_3_source_id_19":{"attribute_name":"ISSN","attribute_value_mlt":[{"subitem_source_identifier":"0386-5924","subitem_source_identifier_type":"PISSN"},{"subitem_source_identifier":"2758-089X","subitem_source_identifier_type":"EISSN"}]},"item_3_text_6":{"attribute_name":"著者所属(日)","attribute_value_mlt":[{"subitem_text_language":"ja","subitem_text_value":"川崎医科大学内科消化器科I部門"}]},"item_3_text_7":{"attribute_name":"著者所属(英)","attribute_value_mlt":[{"subitem_text_language":"en","subitem_text_value":"Division of Gastroenterology, department of Medicine, Kawasaki Medical School"}]},"item_3_textarea_10":{"attribute_name":"抄録(日)","attribute_value_mlt":[{"subitem_textarea_language":"ja","subitem_textarea_value":"近年,肝不全に対する肝補助療法として肝細胞移植や肝機能の中心を担う部分に生物学的素材を用いたバイオ人工肝臓の開発が望まれている.肝細胞療法にしようする細胞はより高い分化肝機能が維持されていることが重要であると考えられる.p21WAF1はcyclin-dependent kinase (CDK) inhibitorであり,特にG1期における細胞周期停止を誘導する事が知られている.また,p21を強制発現させる事で様々な細胞株で分化誘導が示されている.本研究ではSV40T抗原ヒト不死化肝細胞株NKNT-3におけるp21の分化誘導能を検討した.NKNT-3にp21発現アデノウイルスベクター(AdCMVp21, CMVのエンハンサー及びプロモーター下流にp21がインサートされている)およびTAT proteinとp21のfusion protein (pTAT-21)を用いて,p21の形質導入をおこなった.細胞形態,細胞周期,アルブミン発現,薬物代謝酵素であるcytochrome P450関連酵素(CYP)発現い及ぼす効果を検討した.免疫染色およびWestern blottingによってAdCMVp21およびpTATp21による効果的なp21の発現がNKNT-3細胞に認められた.p21形質導入後の細胞は細胞密度は減少し,胞体の増大を認めN/C比の低下が認められた.細胞周期解析ではG1 arrestの状態となった.また,アルブミンおよびCYP3A4, Cyp2c9の発現増強が認められた.ヒト不死化肝細胞(NKNT-3)にp21を過剰発現させることによる分化機能誘導が可能であることが示唆された."}]},"item_3_textarea_11":{"attribute_name":"抄録(英)","attribute_value_mlt":[{"subitem_textarea_language":"en","subitem_textarea_value":"Recently, there has been great expectation regarding the use of cell therapies such as hepatocyte transplantation and bioartificial livers to treat patients with liver failure. Improvement of differentiated cellular functions is of fundamental importance in hepatocyte-based biological therapies. The molecule of p21, known as WAF1, is a potent cyclin-dependent kinase inhibitor which regulates the transition from the G1 phase to the S phase in a cell cycle. Investigators have demonstrated that p21 transduction induces cellular differentiation in various cell lines, We used SV40Tag-immortalized human NKNT-3 hepatocytes in this study. A replication-deficient adenovirus vector, Ad5CMVp21, expressing a p21 gene under the control of the CMV promoter, was used to achieve efficient p21 delivery. A pTAT-p21 fusion protein was also utilized for transduction in NKNT-3 cells. Morphological alteration, cell-cycle progression, and protein expression of albumin, CYP3A4, and CYP2C8 were analyzed in the p21-transduced NKNT-3 cells. Immuofluorescent staining and Western blotting analysis for p21 showed efficient p21 transduction in the NKNT-3 cells using Ad5CMVp21 or pTAT-p21. Under cell cycle analysis, transduction of p21 caused G1-arrest in NKNT-3 cells leading to differentiated hepatic phenotypes including a decreased N-C (nucleo-cytoplasmic) ratio, decreased cell density, and enhanced protein expression of albumin, CYP3A4, and CYP2C9. In the results persented here, we show that exogenous expression of p21 augmented cellular differentiation in immortalized human NKNT-3 cells."}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"國枝, 武美","creatorNameLang":"ja"},{"creatorName":"クニエダ, タケミ","creatorNameLang":"ja-Kana"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"KUNIEDA, Takemi","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":"2017-01-23"}],"displaytype":"detail","filename":"KJ00001725523.pdf","filesize":[{"value":"1.1 MB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"KJ00001725523.pdf","objectType":"fulltext","url":"https://kwmed.repo.nii.ac.jp/record/1264/files/KJ00001725523.pdf"},"version_id":"ab2fe681-163b-476c-8ff2-37bb81602d33"}]},"item_keyword":{"attribute_name":"キーワード","attribute_value_mlt":[{"subitem_subject":"p21","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"Immmortalized human hepatocyte","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"Differentiation","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"TAT protain","subitem_subject_language":"en","subitem_subject_scheme":"Other"}]},"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":"journal article","resourceuri":"http://purl.org/coar/resource_type/c_6501"}]},"item_title":"p21によるヒト肝細胞株での分化誘導療法の開発","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"p21によるヒト肝細胞株での分化誘導療法の開発","subitem_title_language":"ja"},{"subitem_title":"p21 Transduction Augments Differentiated Phenotypes in Immortalized Human Hepatocytes","subitem_title_language":"en"}]},"item_type_id":"3","owner":"31","path":["505"],"pubdate":{"attribute_name":"PubDate","attribute_value":"2017-01-23"},"publish_date":"2017-01-23","publish_status":"0","recid":"1264","relation_version_is_last":true,"title":["p21によるヒト肝細胞株での分化誘導療法の開発"],"weko_creator_id":"31","weko_shared_id":-1},"updated":"2024-04-18T04:05:10.786512+00:00"}