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

研究成果: Article査読

39 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)706-711
ページ数6
ジャーナルBiochemical and Biophysical Research Communications
376
4
DOI
出版ステータスPublished - 28-11-2008
外部発表はい

All Science Journal Classification (ASJC) codes

  • 生物理学
  • 生化学
  • 分子生物学
  • 細胞生物学

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