{"created":"2023-06-19T07:19:12.458757+00:00","id":5137,"links":{},"metadata":{"_buckets":{"deposit":"bd3996f2-6103-4411-9b37-69e29b5e7127"},"_deposit":{"created_by":4,"id":"5137","owners":[4],"pid":{"revision_id":0,"type":"depid","value":"5137"},"status":"published"},"_oai":{"id":"oai:az.repo.nii.ac.jp:00005137","sets":["17:37:227","17:40:280","31:181:511"]},"author_link":["22291","22292","22294","22293","22289","22290"],"item_12_biblio_info_16":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2007-03-31","bibliographicIssueDateType":"Issued"},"bibliographicPageEnd":"165","bibliographicPageStart":"160","bibliographicVolumeNumber":"13/14","bibliographic_titles":[{"bibliographic_title":"麻布大学雑誌"},{"bibliographic_title":"Journal of Azabu University","bibliographic_titleLang":"en"}]}]},"item_12_description_13":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"TGF-βファミリーに属する分子群は,生命を維持する上で重要と考えられる生物現象の多くに関与しているが,現在知られている情報伝達経路は極めて単純である。したがって,多様な生物活性を惹起するためには,標的細胞の種類に関わらない普遍的な情報伝達機構と標的細胞特異的な情報伝達機構があるものと推測される。そこで,TGF-βファミリーが如何にして多機能を発揮するかを分子レベルで明らかにすることを目的として本研究を行った。本年度は,免疫担当細胞であるマスト細胞を用いて,TGF-βファミリーによる標的細胞特異的な情報伝達についての解析を試みた。マウスの骨髄より調製した前駆マスト細胞(BMMC)においてactivin A(4 nM)刺激2時間後に誘導される遺伝子群を網羅的に解析したところ,CRAL/TRIO並びにGOLDドメインを有するtocopherol-associated protein(Tap) がactivin Aによって誘導されることが明らかになった。activin A刺激によるTap発現の増加は,マスト細胞株であるMC/9においても認められたが,マクロファージ細胞株であるRAW264,メラノーマ細胞株であるB16や胚性腫瘍細胞株であるP19ではactivin A処理によってTapの増加は認められなかった。また,BMMCにおけるTap誘導は,TGF-β_1(200pM)刺激後にも認められたのに対して,BMP-2(4nM)刺激時には認められなかった。一方,activin/TGF-βのI型受容体キナーゼの阻害剤であるSB431542の前処理によってこの遺伝子誘導は減少したが,その程度は,activin/TGF-β誘導性の別の遺伝子群(mmcp-1とmmcp-7)のSB431542による抑制に比べて小さいものであった。Tapがactivin/TGF-β刺激によって誘導されることの意義を調べるため,activin/TGF-β responsive reporterを用いて解析したところ,Tap存在下によってactivin/TGF-β シグナルは増強された。Tap発現がactivin/TGF-βによって誘導されるのはマスト細胞に特異的であり,誘導されたTapはactivin/TGF-βシグナルの増強因子であると考えられた。","subitem_description_type":"Abstract"}]},"item_12_description_14":{"attribute_name":"Abstract","attribute_value_mlt":[{"subitem_description":"In order to gain better understanding on multifunction of pluripotent TGF-β family members at the molecular level, the genes that were up-regulated in response to treatment with members of the TGF-β family were investigated in mouse bone marrow-derived cultured mast cells (BMMC). The cDNA microarray analyses indicated that in BMMC, five genes were induced by treatment with 4nM activin A, a member of the TGF-β family, for 2h. Tocopherol-associated protein (Tap) was one of the induced genes, and the Tap induction in response to activin A treatment was confirmed by competitive RT-PCR and real-time RT-PCR analyses. Treatment with TGF-β_1 at 200pM but not BMP-2 at 4nM also increased Tap gene transcript in BMMC. Activin A-induced Tap expression was detected in BMMC and MC/9 mast cells but not in RAW264 macrophage-like cells, B16 melanoma cells or P19 embryonic carcinoma cells. Treatment with > 1 μM SB431542, an inhibitor of activin and TGF-β type I receptors ALK4/5, reduced responsiveness of Tap expression to TGF-β_1, whereas < 0.5 μM SB431542 effectively reduced TGF-β_1-induced expression of mmcp-1 and mmcp-7. Induction of Tap was also detected in BMMC from Smad3-null mice, although the levels were lower than observed with wild-type mice. These results suggest that Tap is induced not only through an activated ALK4/5- and Smad3-mediated mechanism but also through an ALK4/5-independent mechanism. Reporter assays indicated that Tap expression enhances transcription mediated by the activin/TGF-β pathway. Thus, the present results suggest that Tap induction in response to activin/TGF-β occurs predominantly in mast cells and serves as a positive regulator in activin/TGF-β signaling.","subitem_description_type":"Other"}]},"item_12_description_2":{"attribute_name":"ページ属性","attribute_value_mlt":[{"subitem_description":"P(論文)","subitem_description_type":"Other"}]},"item_12_description_3":{"attribute_name":"記事種別","attribute_value_mlt":[{"subitem_description":"特集","subitem_description_type":"Other"}]},"item_12_description_34":{"attribute_name":"format","attribute_value_mlt":[{"subitem_description":"application/pdf","subitem_description_type":"Other"}]},"item_12_description_4":{"attribute_name":"Type","attribute_value_mlt":[{"subitem_description":"FEATURE ARTICLES","subitem_description_type":"Other"}]},"item_12_publisher_19":{"attribute_name":"出版者","attribute_value_mlt":[{"subitem_publisher":"麻布大学"}]},"item_12_publisher_20":{"attribute_name":"Publisher","attribute_value_mlt":[{"subitem_publisher":"Azabu University"}]},"item_12_source_id_21":{"attribute_name":"ISSN","attribute_value_mlt":[{"subitem_source_identifier":"1346-5880","subitem_source_identifier_type":"ISSN"}]},"item_12_source_id_23":{"attribute_name":"書誌レコードID","attribute_value_mlt":[{"subitem_source_identifier":"AA11561468","subitem_source_identifier_type":"NCID"}]},"item_12_text_10":{"attribute_name":"Author ID","attribute_value_mlt":[{"subitem_text_value":"-"},{"subitem_text_value":"000065"},{"subitem_text_value":"000259"}]},"item_12_text_11":{"attribute_name":"所属機関","attribute_value_mlt":[{"subitem_text_value":"麻布大学獣医学部栄養学研究室"},{"subitem_text_value":"麻布大学獣医学部微生物学第一研究室"},{"subitem_text_value":"麻布大学獣医学部分子生物学研究室"}]},"item_12_text_12":{"attribute_name":"Institution or Company","attribute_value_mlt":[{"subitem_text_value":"Laboratories of Nutrition, Azabu University School of Veterinary Medicine"},{"subitem_text_value":"Laboratories of Veterinary Microbiology I, Azabu University School of Veterinary Medicine"},{"subitem_text_value":"Laboratories of Molecular Biology, Azabu University School of Veterinary Medicine"}]},"item_12_text_9":{"attribute_name":"著者ID","attribute_value_mlt":[{"subitem_text_value":"-"},{"subitem_text_value":"000065"},{"subitem_text_value":"000259"}]},"item_12_version_type_29":{"attribute_name":"著者版フラグ","attribute_value_mlt":[{"subitem_version_resource":"http://purl.org/coar/version/c_970fb48d4fbd8a85","subitem_version_type":"VoR"}]},"item_12_version_type_30":{"attribute_name":"text version","attribute_value_mlt":[{"subitem_version_resource":"http://purl.org/coar/version/c_970fb48d4fbd8a85","subitem_version_type":"VoR"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"舟場, 正幸"},{"creatorName":"フナバ, マサユキ","creatorNameLang":"ja-Kana"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"池田, 輝雄"},{"creatorName":"イケダ, テルオ","creatorNameLang":"ja-Kana"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"村上, 賢"},{"creatorName":"ムラカミ, マサル","creatorNameLang":"ja-Kana"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Funaba, Masayuki","creatorNameLang":"en"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Ikeda, Teruo","creatorNameLang":"en"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Murakami, Masaru","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":"2006-01-01"}],"displaytype":"detail","filename":"bull_jau_vol13-14-160.pdf","filesize":[{"value":"493.1 kB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"bull_jau_vol13-14-160.pdf","url":"https://az.repo.nii.ac.jp/record/5137/files/bull_jau_vol13-14-160.pdf"},"version_id":"52ed14a1-89a9-415c-87a7-8f3211244cef"}]},"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":"departmental bulletin paper","resourceuri":"http://purl.org/coar/resource_type/c_6501"}]},"item_title":"多機能分子群であるTGF-βファミリーが多機能である理由 : シグナル伝達の観点からの検討","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"多機能分子群であるTGF-βファミリーが多機能である理由 : シグナル伝達の観点からの検討"},{"subitem_title":"Molecular bases of multifunction of pluripotent TGF-β family members with emphasis on signal transduction","subitem_title_language":"en"}]},"item_type_id":"12","owner":"4","path":["227","280","511"],"pubdate":{"attribute_name":"公開日","attribute_value":"2006-01-01"},"publish_date":"2006-01-01","publish_status":"0","recid":"5137","relation_version_is_last":true,"title":["多機能分子群であるTGF-βファミリーが多機能である理由 : シグナル伝達の観点からの検討"],"weko_creator_id":"4","weko_shared_id":4},"updated":"2023-06-19T07:50:10.410726+00:00"}