Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 706-711 |
| Number of pages | 6 |
| Journal | Biochemical and Biophysical Research Communications |
| Volume | 376 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - 28-11-2008 |
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All Science Journal Classification (ASJC) codes
- Biophysics
- Biochemistry
- Molecular Biology
- Cell Biology
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Activated macrophages down-regulate podocyte nephrin and podocin expression via stress-activated protein kinases. / Ikezumi, Yohei; Suzuki, Toshiaki; Karasawa, Tamaki; Kawachi, Hiroshi; Nikolic-Paterson, David J.; Uchiyama, Makoto.
In: Biochemical and Biophysical Research Communications, Vol. 376, No. 4, 28.11.2008, p. 706-711.Research output: Contribution to journal › Article
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
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.
UR - http://www.scopus.com/inward/record.url?scp=53449093804&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=53449093804&partnerID=8YFLogxK
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 -