Activated macrophages down-regulate podocyte nephrin and podocin expression via stress-activated protein kinases

Yohei Ikezumi, Toshiaki Suzuki, Tamaki Karasawa, Hiroshi Kawachi, David J. Nikolic-Paterson, Makoto Uchiyama

Research output: Contribution to journalArticle

33 Citations (Scopus)

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 languageEnglish
Pages (from-to)706-711
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume376
Issue number4
DOIs
Publication statusPublished - 28-11-2008

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Podocytes
Macrophages
Heat-Shock Proteins
Protein Kinases
Down-Regulation
Conditioned Culture Medium
Kidney Diseases
JNK Mitogen-Activated Protein Kinases
Wounds and Injuries
Rats
Neutralizing Antibodies
Proteinuria
Phosphotransferases
NPHS2 protein
nephrin
Anti-Idiotypic Antibodies
Messenger RNA
Antibodies
Kidney
Proteins

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Ikezumi, Yohei ; Suzuki, Toshiaki ; Karasawa, Tamaki ; Kawachi, Hiroshi ; Nikolic-Paterson, David J. ; Uchiyama, Makoto. / Activated macrophages down-regulate podocyte nephrin and podocin expression via stress-activated protein kinases. In: Biochemical and Biophysical Research Communications. 2008 ; Vol. 376, No. 4. pp. 706-711.
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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 journalArticle

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