Transcriptional suppression of nephrin in podocytes by macrophages: Roles of inflammatory cytokines and involvement of the PI3K/Akt pathway

被引：90

作者：

Takano, Yosuke ^{[1
]}

Yamauchi, Kozue ^{[1
]}

Hayakawa, Kunihiro ^{[1
]}

Hiramatsu, Nobuhiko ^{[1
]}

Kasai, Ayumi ^{[1
]}

Okamura, Maro ^{[1
]}

Yokouchi, Makiko ^{[1
]}

Shitamura, Akihiro ^{[1
]}

Yao, Han ^{[1
]}

Kitamura, Masanori ^{[1
]}

机构：

[1] Univ Yamanashi, Interdisciplinary Grad Sch Med & Engn, Dept Mol Signaling, Yamanashi 4093898, Japan

来源：

FEBS LETTERS | 2007年 / 581卷 / 03期

关键词：

podocyte; nephrin; macrophage; IL-1; beta; TNF-alpha; phosphatidylinositol-3-kinase;

D O I：

10.1016/j.febslet.2006.12.051

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Expression of nephrin, a crucial component of the glomerular slit diaphragm, is downregulated in patients with proteinuric glomerular diseases. Using conditionally immortalized reporter podocytes, we found that bystander macrophages as well as macrophage-derived cytokines IL-1 beta and TNF-alpha markedly suppressed activity of the nephrin gene promoter in podocytes. The cytokine-initiated repression was reversible, observed on both basal and inducible expression, independent of Wilms' tumor suppressor WT1, and caused in part via activation of the phosphatidylinositol-3-kinase/Akt pathway. These results indicated a novel mechanism by which activated macrophages participate in the induction of proteinuria in glomerular diseases. (c) 2007 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

引用

页码：421 / 426

页数：6

共 32 条

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