A Combination of an Angiotensin II Receptor and a Neprilysin Inhibitor Attenuates Liver Fibrosis by Preventing Hepatic Stellate Cell Activation

• 資料種別: 博士論文
• タイトル: A Combination of an Angiotensin II Receptor and a Neprilysin Inhibitor Attenuates Liver Fibrosis by Preventing Hepatic Stellate Cell Activation
• 著者・編者: Suzuki, Junya; Kaji, Kosuke; Nishimura, Norihisa; Kubo, Takahiro; Tomooka, Fumimasa; Shibamoto, Akihiko; Iwai, Satoshi; Tsuji, Yuki; Fujinaga, Yukihisa; Kitagawa, Koh; Namisaki, Tadashi; Akahane, Takemi; Yoshiji, Hitoshi
• 著者標目: Suzuki, Junya; Kaji, Kosuke; Nishimura, Norihisa; Kubo, Takahiro; Tomooka, Fumimasa; Shibamoto, Akihiko; Iwai, Satoshi; Tsuji, Yuki; Fujinaga, Yukihisa; Kitagawa, Koh; Namisaki, Tadashi; Akahane, Takemi; Yoshiji, Hitoshi
• 出版事項: MDPI
• 出版年月日等: 2023-04; 11 5
• 出版年（W3CDTF）: 2023-04
• 並列タイトル等: アンジオテンシンⅡ受容体拮抗剤とネプリライシン阻害剤の併用が肝星状細胞の活性化を抑制し，肝線維化を抑制する
• 授与機関名: 奈良県立医科大学
• 授与年月日: 2024-03-14
• 授与年月日（W3CDTF）: 2024-03-14
• 報告番号: 甲第914号
• 学位: 博士（医学）
• 本文の言語コード: eng
• 件名標目: liver fibrosis; hepatic stellate cell; natriuretic peptide; angiotensin II
• 対象利用者: 一般
• 一般注記: type:Thesis; The renin-angiotensin-aldosterone system has gained attention due to its role as a mediator of liver fibrosis and hepatic stellate cell (HSC) activation. Meanwhile, the natriuretic peptide (NP) system, including atrial NP (ANP) and C-type NP (CNP), is a counter-regulatory hormone regulated by neprilysin. Although the combination of an angiotensin receptor and a neprilysin inhibitor (sacubitril/valsartan: SAC/VAL) has shown clinical efficacy in patients with heart failure, its potential effects on hepatic fibrosis have not been clarified. This study assessed the effects of SAC/VAL in carbon tetrachloride (CCl4)-induced murine liver fibrosis as well as the in vitro phenotypes of HSCs. Treatment with SAC and VAL markedly attenuated CCl4-induced liver fibrosis while reducing α-SMA+-HSC expansion and decreasing hepatic hydroxyproline and mRNA levels of pro-fibrogenic markers. Treatment with SAC increased plasma ANP and CNP levels in CCl4-treated mice, and ANP effectively suppressed cell proliferation and TGF-β-stimulated MMP2 and TIMP2 expression in LX-2 cells by activating guanylate cyclase-A/cGMP/protein kinase G signaling. Meanwhile, CNP did not affect the pro-fibrogenic activity of LX-2 cells. Moreover, VAL directly inhibited angiotensin II (AT-II)-stimulated cell proliferation and the expression of TIMP1 and CTGF through the blockade of the AT-II type 1 receptor/protein kinase C pathway. Collectively, SAC/VAL may be a novel therapeutic treatment for liver fibrosis.; 権利情報：© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).; identifier:Biomedicines. 2023 Apr, vol.11, no.5, article no.1295; identifier:2227-9059; identifier:http://ginmu.naramed-u.ac.jp/dspace/handle/10564/4365; identifier:Biomedicines, 11(5): 1295
• 国立国会図書館永続的識別子: info:ndljp/pid/13722125; https://dl.ndl.go.jp/pid/13722125
• コレクション（共通）: 障害者向け資料
• コレクション（障害者向け資料：レベル1）: テキストデータ
• コレクション（個別）: 国立国会図書館デジタルコレクション > デジタル化資料 > 博士論文; https://dl.ndl.go.jp/collections/A00014
• 収集根拠: 博士論文（自動収集）
• 受理日（W3CDTF）: 2024-07-05T22:06:56+09:00
• 記録形式（IMT）: application/pdf
• オンライン閲覧公開範囲: 国立国会図書館内限定公開
• デジタル化資料送信: 図書館・個人送信対象外
• 遠隔複写可否（NDL）: 可
• 掲載誌（URI）: http://hdl.handle.net/10564/4365
• 連携機関・データベース: 国立国会図書館 : 国立国会図書館デジタルコレクション; https://dl.ndl.go.jp