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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
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
キーワード
Extracellular signal-regulated kinase
glomerulonephritis
renin-angiotensin system
macrophage infiltration
fibrosis
資料タイプ
学位論文
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
ISSN
14401797
cat書誌ID
AA1163047X
出版者
Asian Pacific Society of Nephrology|Wiley
21
11
開始ページ
950
終了ページ
958
発行日
2015-12-01
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
著者版フラグ
博士論文全文を含む
文科省報告番号
甲第2905号
学位記番号
甲医第1279号
学位授与年月日
2016-03-07
学位名
博士(医学)
学位授与機関
徳島大学
部局
病院
医学系