TY - JOUR
T1 - Activated macrophages down-regulate podocyte nephrin and podocin expression via stress-activated protein kinases
AU - Ikezumi, Yohei
AU - Suzuki, Toshiaki
AU - Karasawa, Tamaki
AU - Kawachi, Hiroshi
AU - Nikolic-Paterson, David J.
AU - Uchiyama, Makoto
N1 - Funding Information:
This work was supported by Grant-Aids for Scientific Research (C) (No.19591242) from the Ministry of Education, Culture, Sports, Science and Technology of Japan, the Study Group on IgA nephropathy, and Grant-Aids for Promotion of Niigata University Research Projects from Niigata University.
PY - 2008/11/28
Y1 - 2008/11/28
N2 - The development of proteinuria and glomerulosclerosis in kidney disease is associated with podocyte damage, including down-regulation of nephrin and podocin. Macrophages are known to induce renal injury, but the mechanisms involved are not fully understood. This study examined macrophage-mediated podocyte damage. Conditioned media (CM) from activated macrophages caused a 50-60% reduction in nephrin and podocin mRNA and protein expression in cultured mouse podocytes and rat glomeruli. This was abolished by a neutralizing anti-TNFα antibody. The addition of recombinant TNFα to podocytes or glomeruli caused a comparable reduction in podocyte nephrin and podocin expression to that of macrophage CM. Inhibition of c-Jun amino terminal kinase (JNK) or p38 kinase abolished the TNFα-induced reduction in nephrin and podocin expression. This study demonstrates that activated macrophages can induce podocyte injury via a TNFα-JNK/p38-dependent mechanism. This may explain, in part, the protective effects of JNK and p38 blockade in experimental kidney disease.
AB - The development of proteinuria and glomerulosclerosis in kidney disease is associated with podocyte damage, including down-regulation of nephrin and podocin. Macrophages are known to induce renal injury, but the mechanisms involved are not fully understood. This study examined macrophage-mediated podocyte damage. Conditioned media (CM) from activated macrophages caused a 50-60% reduction in nephrin and podocin mRNA and protein expression in cultured mouse podocytes and rat glomeruli. This was abolished by a neutralizing anti-TNFα antibody. The addition of recombinant TNFα to podocytes or glomeruli caused a comparable reduction in podocyte nephrin and podocin expression to that of macrophage CM. Inhibition of c-Jun amino terminal kinase (JNK) or p38 kinase abolished the TNFα-induced reduction in nephrin and podocin expression. This study demonstrates that activated macrophages can induce podocyte injury via a TNFα-JNK/p38-dependent mechanism. This may explain, in part, the protective effects of JNK and p38 blockade in experimental kidney disease.
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U2 - 10.1016/j.bbrc.2008.09.049
DO - 10.1016/j.bbrc.2008.09.049
M3 - Article
C2 - 18809387
AN - SCOPUS:53449093804
VL - 376
SP - 706
EP - 711
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 4
ER -