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  1. C100 医学部/医学系研究科
  2. C100a 雑誌掲載論文
  3. 学術雑誌

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/2237/00028573
36039e53-7854-4f65-83b6-dfafcf168303
名前 / ファイル ライセンス アクション
BBI-D-17-00406R1.pdf BBI-D-17-00406R1 (1.5 MB)
Item type 学術雑誌論文 / Journal Article(1)
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

WEKO 85290

en Yisireyili, Maimaiti

Search repository
Uchida, Yasuhiro

× Uchida, Yasuhiro

WEKO 85291

en Uchida, Yasuhiro

Search repository
Yamamoto, Koji

× Yamamoto, Koji

WEKO 85292

en Yamamoto, Koji

Search repository
Nakayama, Takayuki

× Nakayama, Takayuki

WEKO 85293

en Nakayama, Takayuki

Search repository
Cheng, Xian Wu

× Cheng, Xian Wu

WEKO 85294

en Cheng, Xian Wu

Search repository
Matsushita, Tadashi

× Matsushita, Tadashi

WEKO 85295

en Matsushita, Tadashi

Search repository
Nakamura, Shigeo

× Nakamura, Shigeo

WEKO 85296

en Nakamura, Shigeo

Search repository
Murohara, Toyoaki

× Murohara, Toyoaki

WEKO 85297

en Murohara, Toyoaki

Search repository
Takeshita, Kyosuke

× Takeshita, Kyosuke

WEKO 85298

en Takeshita, Kyosuke

Search repository
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
著者版フラグ
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