RRC ID |
42868
|
Author |
Takano Y, Yamauchi K, Hayakawa K, Hiramatsu N, Kasai A, Okamura M, Yokouchi M, Shitamura A, Yao J, Kitamura M.
|
Title |
Transcriptional suppression of nephrin in podocytes by macrophages: roles of inflammatory cytokines and involvement of the PI3K/Akt pathway.
|
Journal |
FEBS Lett
|
Abstract |
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-1beta 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.
|
Volume |
581(3)
|
Pages |
421-6
|
Published |
2007-2-6
|
DOI |
10.1016/j.febslet.2006.12.051
|
PII |
S0014-5793(07)00020-8
|
PMID |
17239861
|
MeSH |
Animals
Cell Communication
Cells, Cultured
Cytokines / metabolism
Cytokines / pharmacology
Down-Regulation / drug effects
Humans
Inflammation Mediators / metabolism
Inflammation Mediators / pharmacology
Interleukin-1beta / metabolism
Interleukin-1beta / pharmacology
Macrophages / immunology
Macrophages / metabolism*
Membrane Proteins / genetics*
Mice
Phosphatidylinositol 3-Kinases / metabolism
Podocytes / drug effects
Podocytes / metabolism*
Promoter Regions, Genetic
Proto-Oncogene Proteins c-akt / metabolism
Tumor Necrosis Factor-alpha / metabolism
Tumor Necrosis Factor-alpha / pharmacology
|
IF |
3.057
|
Times Cited |
65
|
WOS Category
|
BIOPHYSICS
BIOCHEMISTRY & MOLECULAR BIOLOGY
CELL BIOLOGY
|
Resource |
Human and Animal Cells |
J774.1(RCB0434) |