Differential regulation of angiotensin II-induced extracellular signal regulated kinase-1/2 and -5 in progressive glomerulonephritis

• 資料種別: 博士論文
• ISSN: 1440-1797
• タイトル: Differential regulation of angiotensin II-induced extracellular signal regulated kinase-1/2 and -5 in progressive glomerulonephritis
• 巻次・部編番号: 21 11
• 著者・編者: Nagai, Takashi; Urushihara, Maki; Kinoshita, Yukiko; Jamba, Ariunbold; Kondo, Shuji; Kagami, Shoji
• 著者標目: Nagai, Takashi; Urushihara, Maki; Kinoshita, Yukiko; Jamba, Ariunbold; Kondo, Shuji; Kagami, Shoji
• 出版事項: Asian Pacific Society of Nephrology|Wiley
• 出版年月日等: 2015-12-01
• 出版年（W3CDTF）: 2015-12-01
• 並列タイトル等: 進行性腎炎におけるアンジオテンシンIIにより活性化された細胞外シグナル調節キナーゼ-1/2および5の病態制御機構; Role of ERK1/2 and ERK5 in glomerulonephritis
• タイトル（掲載誌）: Nephrology
• 授与機関名: 徳島大学
• 授与年月日: 2016-03-07
• 授与年月日（W3CDTF）: 2016-03-07
• 報告番号: 甲第2905号
• 学位: 博士（医学）
• 博論授与番号: 甲第2905号
• 本文の言語コード: eng
• 件名標目: Extracellular signal-regulated kinase; glomerulonephritis; renin-angiotensin system; macrophage infiltration; fibrosis
• 対象利用者: 一般
• 一般注記: Aim: Extracellular signal regulated kinase (ERK)1/2 and ERK5 are key kinases of the signaling pathways involved in various cellular responses to kidney injury; however, the mechanistic links between those kinase and renin-angiotensin system (RAS) activation in glomerulonephritis (GN) have not been fully elucidated. In this study, we sought to clarify the potential roles of ERK1/2 and ERK5 via RAS activation in the pathogenesis of GN.Methods: A rat model of progressive GN was induced by anti-glomerular basement membrane (GBM) injection and the signal transduction pathway in angiotensin II (Ang II)-induced glomerular pathologic alterations were investigated in primary cultured mesangial cells (MCs). Results: Rats developed typical cellular crescents in glomeruli on day 7 that progressed to severe fibrocellular crescents and glomerulosclerosis on day 28. Strong expression of phospho-ERK1/2 was observed on day 7 and phospho-ERK5 expression was markedly increased on day 28 of GN. An angiotensin II type 1 receptor blocker (ARB) suppressed those augmentations. Moreover, ARB treatment attenuated the increases in macrophage infiltration and PCNA-positive cells observed on day 7 in GN rats, as well as the increase in collagen type 1 expression on day 28. Consistently, MCs stimulated by Ang II showed significant increases in proliferation and the expression of MCP-1 and collagen type 1. Interestingly, while the ERK1/2 inhibitor PD98059 abolished the elevations in MCP-1 expression and cell proliferation, the ERK5 inhibitor BIX02189 abrogated the elevation in collagen type 1 expression.Conclusion: Altogether, these data suggest that ERK1/2 regulates acute inflammatory reactions, while ERK5 promotes the development of RAS-induced chronic glomerular fibrosis activation in GN.
• DOI: info:doi/10.1111/nep.12685; https://doi.org/info:doi/10.1111/nep.12685
• 国立国会図書館永続的識別子: info:ndljp/pid/11115872; https://dl.ndl.go.jp/pid/11115872
• 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）: 2018-07-03T21:49:10+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://repo.lib.tokushima-u.ac.jp/109686
• 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