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ID 109686
Title Alternative
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
Author
Nagai, Takashi Tokushima University
Jamba, Ariunbold Tokushima University
Keywords
Extracellular signal-regulated kinase
glomerulonephritis
renin-angiotensin system
macrophage infiltration
fibrosis
Content Type
Thesis or Dissertation
Description
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.
Journal Title
Nephrology
ISSN
14401797
NCID
AA1163047X
Publisher
Asian Pacific Society of Nephrology|Wiley
Volume
21
Issue
11
Start Page
950
End Page
958
Published Date
2015-12-01
Remark
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
DOI (Published Version)
URL ( Publisher's Version )
FullText File
language
eng
TextVersion
ETD
MEXT report number
甲第2905号
Diploma Number
甲医第1279号
Granted Date
2016-03-07
Degree Name
Doctor of Medical Science
Grantor
Tokushima University
departments
University Hospital
Medical Sciences