{"created":"2023-03-07T05:13:32.480933+00:00","id":2000825,"links":{},"metadata":{"_buckets":{"deposit":"ff623d10-ec73-4a74-9c60-c0f1e81d1795"},"_deposit":{"id":"2000825","owners":[1],"pid":{"revision_id":0,"type":"depid","value":"2000825"},"status":"published"},"_oai":{"id":"oai:niigata-u.repo.nii.ac.jp:02000825","sets":["453:455","471:561:562"]},"author_link":[],"control_number":"2000825","item_6_date_granted_51":{"attribute_name":"学位授与年月日","attribute_value_mlt":[{"subitem_dategranted":"2022-03-23"}]},"item_6_degree_grantor_49":{"attribute_name":"学位授与機関","attribute_value_mlt":[{"subitem_degreegrantor":[{"subitem_degreegrantor_language":"ja","subitem_degreegrantor_name":"新潟大学"},{"subitem_degreegrantor_language":"en","subitem_degreegrantor_name":"Niigata University"}],"subitem_degreegrantor_identifier":[{"subitem_degreegrantor_identifier_name":"13101","subitem_degreegrantor_identifier_scheme":"kakenhi"}]}]},"item_6_degree_name_48":{"attribute_name":"学位名","attribute_value_mlt":[{"subitem_degreename":"博士（医学）","subitem_degreename_language":"ja"}]},"item_6_description_4":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"The liver has a high regenerative ability and can induce spontaneous regression of fibrosis when early liver damage occurs; however, these abilities are lost when chronic liver damage results in decompensated cirrhosis. Cell therapies, such as mesenchymal stem cell (MSC) and macrophage therapies, have attracted attention as potential strategies for mitigating liver fibrosis. Here, we evaluated the therapeutic effects of HMGB1 peptide synthesized from box A of high mobility group box 1 protein. Liver damage and fibrosis were evaluated using a carbon tetrachloride (CCl4)-induced cirrhosis mouse model. The effects of HMGB1 peptide against immune cells were evaluated by single-cell RNA-seq using liver tissues, and those against monocytes/macrophages were further evaluated by in vitro analyses. Administration of HMGB1 peptide did not elicit a rapid response within 36 h, but attenuated liver damage after 1 week and suppressed fibrosis after 2 weeks. Fibrosis regression developed over time, despite continuous liver damage, suggesting that administration of this peptide could induce fibrolysis. In vitro analyses could not confirm a direct effect of HMGB1 peptide against monocyte/macrophages. However, macrophages were the most affected immune cells in the liver, and the number of scar-associated macrophages (Trem2+Cd9+ cells) with anti-inflammatory markers increased in the liver following HMGB1 treatment, suggesting that indirect effects of monocytes/macrophages were important for therapeutic efficacy. Overall, we established a new concept for cell-free therapy using HMGB1 peptide for cirrhosis through the induction of anti-inflammatory macrophages.","subitem_description_language":"en","subitem_description_type":"Abstract"}]},"item_6_description_5":{"attribute_name":"内容記述","attribute_value_mlt":[{"subitem_description":"Inflammation and regeneration. 2021, 41(1), 28.","subitem_description_language":"en","subitem_description_type":"Other"}]},"item_6_description_53":{"attribute_name":"学位記番号","attribute_value_mlt":[{"subitem_description":"新大院博(医)第1039号","subitem_description_language":"ja","subitem_description_type":"Other"}]},"item_6_dissertation_number_52":{"attribute_name":"学位授与番号","attribute_value_mlt":[{"subitem_dissertationnumber":"甲第4969号"}]},"item_6_relation_14":{"attribute_name":"DOI","attribute_value_mlt":[{"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://doi.org/10.1186/s41232-021-00177-4","subitem_relation_type_select":"DOI"}}]},"item_6_rights_15":{"attribute_name":"権利","attribute_value_mlt":[{"subitem_rights":"© The Author(s). 2021","subitem_rights_language":"en"},{"subitem_rights":"Creative Commons Attribution 4.0 International","subitem_rights_language":"en","subitem_rights_resource":"https://creativecommons.org/licenses/by/4.0/"}]},"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":"Nojiri, Shunsuke","creatorNameLang":"en"},{"creatorName":"野尻, 俊介","creatorNameLang":"ja"}]}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_access","date":[{"dateType":"Available","dateValue":"2023-03-07"}],"displaytype":"detail","filename":"r3nmk1039.pdf","filesize":[{"value":"5.82MB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"本文","objectType":"fulltext","url":"https://niigata-u.repo.nii.ac.jp/record/2000825/files/r3nmk1039.pdf"},"version_id":"4cfd1f07-cf75-4bc9-aec6-2d566d1d08bc"},{"accessrole":"open_access","date":[{"dateType":"Available","dateValue":"2023-03-07"}],"displaytype":"detail","filename":"r3nmk1039_a.pdf","filesize":[{"value":"557KB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"要旨","objectType":"abstract","url":"https://niigata-u.repo.nii.ac.jp/record/2000825/files/r3nmk1039_a.pdf"},"version_id":"6111b05e-9d30-4e4d-98e1-51f275c47329"}]},"item_keyword":{"attribute_name":"キーワード","attribute_value_mlt":[{"subitem_subject":"HMGB1","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"Peptide","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"Liver","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"Cirrhosis","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"Fibrosis","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"Mesenchymal stem cell","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"Macrophage","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"Mouse","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"Scar-associated macrophage","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"Single-cell transcriptome analysis","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":"Synthesized HMGB1 peptide attenuates liver inflammation and suppresses fibrosis in mice","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"Synthesized HMGB1 peptide attenuates liver inflammation and suppresses fibrosis in mice","subitem_title_language":"en"},{"subitem_title":"HMGB1合成部分ペプチドはマウスモデル肝において抗炎症・抗線維化作用を表す","subitem_title_language":"ja"}]},"item_type_id":"6","owner":"1","path":["455","562"],"pubdate":{"attribute_name":"PubDate","attribute_value":"2023-03-07"},"publish_date":"2023-03-07","publish_status":"0","recid":"2000825","relation_version_is_last":true,"title":["Synthesized HMGB1 peptide attenuates liver inflammation and suppresses fibrosis in mice"],"weko_creator_id":"1","weko_shared_id":-1},"updated":"2023-04-10T02:51:42.808993+00:00"}