ID | 109686 |
タイトル別表記 | 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
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著者 |
永井, 隆
徳島大学大学院医科学教育部(医学専攻)
Jamba, Ariunbold
Tokushima University
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キーワード | Extracellular signal-regulated kinase
glomerulonephritis
renin-angiotensin system
macrophage infiltration
fibrosis
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資料タイプ |
学位論文
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抄録 | 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. |
掲載誌名 |
Nephrology
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ISSN | 14401797
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cat書誌ID | AA1163047X
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出版者 | Asian Pacific Society of Nephrology|Wiley
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巻 | 21
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号 | 11
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開始ページ | 950
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終了ページ | 958
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発行日 | 2015-12-01
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備考 | 内容要旨・審査要旨・論文本文の公開:
内容要旨・審査要旨 : LID201606071001.pdf 論文本文 : k2905_fulltext.pdf 著者の申請により要約(2016-09-29公開)に替えて論文全文を公開(2018-06-22) 本論文は, 著者Takashi Nagaiの学位論文として提出され, 学位審査・授与の対象となっている。 |
EDB ID | |
出版社版DOI | |
出版社版URL | |
フルテキストファイル | |
言語 |
eng
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著者版フラグ |
博士論文全文を含む
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文科省報告番号 | 甲第2905号
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学位記番号 | 甲医第1279号
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学位授与年月日 | 2016-03-07
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学位名 |
博士(医学)
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学位授与機関 |
徳島大学
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部局 |
病院
医学系
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