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Angiotensin receptor blocker irbesartan reduces stress-induced intestinal inflammation via AT1a signaling and ACE2-dependent mechanism in mice
http://hdl.handle.net/2237/00028573
http://hdl.handle.net/2237/0002857336039e53-7854-4f65-83b6-dfafcf168303
名前 / ファイル | ライセンス | アクション |
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Item type | 学術雑誌論文 / Journal Article(1) | |||||
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公開日 | 2018-09-12 | |||||
タイトル | ||||||
タイトル | Angiotensin receptor blocker irbesartan reduces stress-induced intestinal inflammation via AT1a signaling and ACE2-dependent mechanism in mice | |||||
言語 | en | |||||
著者 |
Yisireyili, Maimaiti
× Yisireyili, Maimaiti× Uchida, Yasuhiro× Yamamoto, Koji× Nakayama, Takayuki× Cheng, Xian Wu× Matsushita, Tadashi× Nakamura, Shigeo× Murohara, Toyoaki× Takeshita, Kyosuke |
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アクセス権 | ||||||
アクセス権 | open access | |||||
アクセス権URI | http://purl.org/coar/access_right/c_abf2 | |||||
権利 | ||||||
言語 | en | |||||
権利情報 | © 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/ | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | Stress | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | Intestinal inflammation | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | Micro-biota | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | Renin-angiotensinogen system | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | Reactive oxygen species | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | Tryptophan metabolism | |||||
抄録 | ||||||
内容記述 | 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. | |||||
言語 | en | |||||
内容記述タイプ | Abstract | |||||
内容記述 | ||||||
内容記述 | ファイル公開:2019-03-01 | |||||
言語 | ja | |||||
内容記述タイプ | Other | |||||
出版者 | ||||||
言語 | en | |||||
出版者 | Elsevier | |||||
言語 | ||||||
言語 | eng | |||||
資源タイプ | ||||||
資源タイプresource | http://purl.org/coar/resource_type/c_6501 | |||||
タイプ | journal article | |||||
出版タイプ | ||||||
出版タイプ | AM | |||||
出版タイプResource | http://purl.org/coar/version/c_ab4af688f83e57aa | |||||
DOI | ||||||
関連タイプ | isVersionOf | |||||
識別子タイプ | DOI | |||||
関連識別子 | https://doi.org/10.1016/j.bbi.2017.11.010 | |||||
ISSN(print) | ||||||
収録物識別子タイプ | PISSN | |||||
収録物識別子 | 0889-1591 | |||||
書誌情報 |
en : Brain, Behavior, and Immunity 巻 69, p. 167-179, 発行日 2018-03 |
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著者版フラグ | ||||||
値 | author |