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Transcriptional suppression of nephrin in podocytes by macrophages: Roles of inflammatory cytokines and involvement of the PI3K/Akt pathway
Author(s) -
Takano Yosuke,
Yamauchi Kozue,
Hayakawa Kunihiro,
Hiramatsu Nobuhiko,
Kasai Ayumi,
Okamura Maro,
Yokouchi Makiko,
Shitamura Akihiro,
Yao Jian,
Kitamura Masanori
Publication year - 2007
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2006.12.051
Subject(s) - nephrin , protein kinase b , pi3k/akt/mtor pathway , slit diaphragm , cancer research , podocyte , microbiology and biotechnology , cytokine , chemistry , proinflammatory cytokine , inflammation , signal transduction , biology , immunology , endocrinology , proteinuria , kidney
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‐1β and TNF‐α 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.