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
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DOI：
10.1016/j.bbrc.2008.09.049
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发表时间：
2008-11-28
影响因子：
3.1
通讯作者：
Uchiyam, Makoto
中科院分区：
文献类型：
--
作者：
Ikezumi, Yohei;Suzuki, Toshiaki;Uchiyam, Makoto
肾脏疾病中蛋白尿和肾小球硬化的发展与足细胞损伤有关，包括neparin和podocin的下调。已知巨噬细胞可引起肾脏损伤，但所涉及的机制尚不完全清楚。这项研究检测了巨噬细胞介导的足细胞损伤。来自活化巨噬细胞的条件培养液(CM)可使培养的小鼠足细胞和大鼠肾小球的neparin和podocin nnRNA和蛋白表达减少50-60%。这一点被中和的抗肿瘤坏死因子α抗体所消除。在肾小球足细胞中加入重组肿瘤坏死因子α后，肾小球足细胞neparin和podocin的表达水平与巨噬细胞CM相似。抑制c-jun氨基末端激酶(JNK)或p38激酶可阻断肿瘤坏死因子α诱导的neparin和podocin表达的减少。本研究表明，活化的巨噬细胞可通过依赖肿瘤坏死因子α-JNK/p38的机制诱导足细胞损伤。这可能在一定程度上解释了JNK和p38阻断对实验性肾脏疾病的保护作用。(C)2008 Elsevier Inc.保留所有权利。
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 nnRNA and protein expression in cultured mouse podocytes and rat glomeruli. This was abolished by a neutralizing anti-TNF alpha antibody. The addition of recombinant TNF alpha to podocytes OF 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 TNF alpha-induced reduction in nephrin and podocin expression. This study demonstrates that activated macrophages can induce podocyte injury via a TNF alpha-JNK/p38-dependent mechanism. This may explain, in part, the protective effects of JNK and p38 blockade in experimental kidney disease. (C) 2008 Elsevier Inc. All rights reserved.