期刊
FEBS LETTERS
卷 581, 期 3, 页码 421-426出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.febslet.2006.12.051
关键词
podocyte; nephrin; macrophage; IL-1 beta; TNF-alpha; phosphatidylinositol-3-kinase
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.
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