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

• Material Type: 博士論文
• ISSN: 1440-1797
• Title: Differential regulation of angiotensin II-induced extracellular signal regulated kinase-1/2 and -5 in progressive glomerulonephritis
• Volume: 21 11
• Author/Editor: Nagai, Takashi; Urushihara, Maki; Kinoshita, Yukiko; Jamba, Ariunbold; Kondo, Shuji; Kagami, Shoji
• Author Heading: Nagai, Takashi; Urushihara, Maki; Kinoshita, Yukiko; Jamba, Ariunbold; Kondo, Shuji; Kagami, Shoji
• Publication, Distribution, etc.: Asian Pacific Society of Nephrology|Wiley
• Publication Date: 2015-12-01
• Publication Date (W3CDTF): 2015-12-01
• Alternative Title: 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
• Periodical title: Nephrology
• Degree grantor/type: 徳島大学
• Date Granted: 2016-03-07
• Date Granted (W3CDTF): 2016-03-07
• Dissertation Number: 甲第2905号
• Degree Type: 博士（医学）
• Conferring No. (Dissertation): 甲第2905号
• Text Language Code: eng
• Subject Heading: Extracellular signal-regulated kinase; glomerulonephritis; renin-angiotensin system; macrophage infiltration; fibrosis
• Target Audience: 一般
• Note (General): 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
• Persistent ID (NDL): info:ndljp/pid/11115872; https://dl.ndl.go.jp/pid/11115872
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• Collection (particular): 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
• Acquisition Basis: 博士論文（自動収集）
• Date Accepted (W3CDTF): 2018-07-03T21:49:10+09:00
• Format (IMT): application/pdf
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• Periodical Title (URI): http://repo.lib.tokushima-u.ac.jp/109686
• Data Provider (Database): 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