کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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1934424 | 1050640 | 2008 | 6 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Activated macrophages down-regulate podocyte nephrin and podocin expression via stress-activated protein kinases Activated macrophages down-regulate podocyte nephrin and podocin expression via stress-activated protein kinases](/preview/png/1934424.png)
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.
Journal: Biochemical and Biophysical Research Communications - Volume 376, Issue 4, 28 November 2008, Pages 706–711