{"created":"2021-03-01T06:34:17.655519+00:00","id":26370,"links":{},"metadata":{"_buckets":{"deposit":"b5e047b4-5b22-499b-a182-8b8ef122b48d"},"_deposit":{"id":"26370","owners":[],"pid":{"revision_id":0,"type":"depid","value":"26370"},"status":"published"},"_oai":{"id":"oai:nagoya.repo.nii.ac.jp:00026370","sets":["499:500:501"]},"author_link":["85290","85291","85292","85293","85294","85295","85296","85297","85298"],"item_10_biblio_info_6":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2018-03","bibliographicIssueDateType":"Issued"},"bibliographicPageEnd":"179","bibliographicPageStart":"167","bibliographicVolumeNumber":"69","bibliographic_titles":[{"bibliographic_title":"Brain, Behavior, and Immunity","bibliographic_titleLang":"en"}]}]},"item_10_description_4":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"Stress is associated with pathophysiology of both irritable bowel syndrome (IBS) and hypertension. Angiotensin receptor blockers (ARB) have anti-inflammatory properties via inhibition of angiotensin II (Ang II)/Ang II type I receptor axis (AT1). Inhibition of the classical RAS pathway is also involved in upregulation of angiotensin converting enzyme-2 (ACE2), which activates the Ang-(1–7)/Mas pathway to counteract inflammatory signaling and acts as a partner of the amino acid transporter, B^0AT-1, to absorb tryptophan for regulation of microbiota-gut-brain axis. In this study, we determined the effects of ARB irbesartan on stress-induced intestinal inflammation. C57BL/6J mice were subjected to 2-week intermittent restraint stress. They were orally treated during the stress with either vehicle, 3 or 10 mg/kg/day irbesartan. Restraint stress resulted in colon inflammation with higher histological damage scores, increased expression of Nox4, TLR-4 and IL1-β, accumulation of reactive oxygen species (ROS), and activation of the ACE–angiotensin II–AT1 receptor axis. Stress also downregulated intestinal amino acid transporter, ACE2/B^0AT-1, and activity of intestinal mammalian target of rapamycin (mTOR) and p70 S6 kinase (p70S6K), resulting in decrease in α-defensins, changes in intestinal microbial contents, and perturbation of tryptophan metabolism with activation of the kynurenine pathway. Administration of irbesartan inhibited activation of stress-induced AT1 pathway to reduce intestinal ROS accumulation and inflammation, restored expression of ACE2/B^0AT-1, activity of mTOR and p70S6K, dysbiosis and tryptophan metabolism. Our results suggest that AT1 is a potentially suitable therapeutic target in stress-induced intestinal inflammation, and that irbesartan could be beneficially suitable for the treatment of stressed patients with IBS.","subitem_description_language":"en","subitem_description_type":"Abstract"}]},"item_10_description_5":{"attribute_name":"内容記述","attribute_value_mlt":[{"subitem_description":"ファイル公開：2019-03-01 ","subitem_description_language":"ja","subitem_description_type":"Other"}]},"item_10_publisher_32":{"attribute_name":"出版者","attribute_value_mlt":[{"subitem_publisher":"Elsevier","subitem_publisher_language":"en"}]},"item_10_relation_11":{"attribute_name":"DOI","attribute_value_mlt":[{"subitem_relation_type":"isVersionOf","subitem_relation_type_id":{"subitem_relation_type_id_text":"https://doi.org/10.1016/j.bbi.2017.11.010","subitem_relation_type_select":"DOI"}}]},"item_10_rights_12":{"attribute_name":"権利","attribute_value_mlt":[{"subitem_rights":"© 2018. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/","subitem_rights_language":"en"}]},"item_10_select_15":{"attribute_name":"著者版フラグ","attribute_value_mlt":[{"subitem_select_item":"author"}]},"item_10_source_id_61":{"attribute_name":"ISSN（print）","attribute_value_mlt":[{"subitem_source_identifier":"0889-1591","subitem_source_identifier_type":"PISSN"}]},"item_1615787544753":{"attribute_name":"出版タイプ","attribute_value_mlt":[{"subitem_version_resource":"http://purl.org/coar/version/c_ab4af688f83e57aa","subitem_version_type":"AM"}]},"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":"Yisireyili, Maimaiti","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"85290","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Uchida, Yasuhiro","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"85291","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Yamamoto, Koji","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"85292","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Nakayama, Takayuki","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"85293","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Cheng, Xian Wu","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"85294","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Matsushita, Tadashi","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"85295","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Nakamura, Shigeo","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"85296","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Murohara, Toyoaki","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"85297","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Takeshita, Kyosuke","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"85298","nameIdentifierScheme":"WEKO"}]}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2019-03-01"}],"displaytype":"detail","filename":"BBI-D-17-00406R1.pdf","filesize":[{"value":"1.5 MB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"BBI-D-17-00406R1","objectType":"fulltext","url":"https://nagoya.repo.nii.ac.jp/record/26370/files/BBI-D-17-00406R1.pdf"},"version_id":"f13269b0-8ab6-4201-9d60-11e567ea7662"}]},"item_keyword":{"attribute_name":"キーワード","attribute_value_mlt":[{"subitem_subject":"Stress","subitem_subject_scheme":"Other"},{"subitem_subject":"Intestinal inflammation","subitem_subject_scheme":"Other"},{"subitem_subject":"Micro-biota","subitem_subject_scheme":"Other"},{"subitem_subject":"Renin-angiotensinogen system","subitem_subject_scheme":"Other"},{"subitem_subject":"Reactive oxygen species","subitem_subject_scheme":"Other"},{"subitem_subject":"Tryptophan metabolism","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":"journal article","resourceuri":"http://purl.org/coar/resource_type/c_6501"}]},"item_title":"Angiotensin receptor blocker irbesartan reduces stress-induced intestinal inflammation via AT1a signaling and ACE2-dependent mechanism in mice","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"Angiotensin receptor blocker irbesartan reduces stress-induced intestinal inflammation via AT1a signaling and ACE2-dependent mechanism in mice","subitem_title_language":"en"}]},"item_type_id":"10","owner":"1","path":["501"],"pubdate":{"attribute_name":"PubDate","attribute_value":"2018-09-12"},"publish_date":"2018-09-12","publish_status":"0","recid":"26370","relation_version_is_last":true,"title":["Angiotensin receptor blocker irbesartan reduces stress-induced intestinal inflammation via AT1a signaling and ACE2-dependent mechanism in mice"],"weko_creator_id":"1","weko_shared_id":-1},"updated":"2023-01-16T04:42:55.827041+00:00"}