High-mobility group box-1 protein promotes granulomatous nephritis in adenine-induced nephropathy.
High-mobility group box-1 protein promotes granulomatous nephritis in adenine-induced nephropathy.
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DOI：
10.1038/labinvest.2010.64
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发表时间：
2010-06
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影响因子：
--
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肉芽肿性肾炎可由多种因素引发并导致肾衰竭。然而，尽管积累了关于肉芽肿性炎症的数据，但肾炎的发病机制仍不清楚。与DNA结合的高迁移率族蛋白盒-1蛋白（HMGB 1）在被激活的巨噬细胞释放时引发并传播炎症，充当组织损伤信号的“警报细胞因子”。在这项研究中，我们证明了在晶体诱导的肉芽肿性肾炎大鼠肾脏肉芽肿中HMGB 1的表达升高，这些大鼠是由富含腺嘌呤的饮食引起的。尿液和血清中的HMGB 1水平以及单核细胞趋化蛋白-1（MCP-1）（肉芽肿性炎症的介质）也升高。在晶体诱导的肉芽肿性肾炎大鼠中，注射HMGB 1使肾功能恶化并上调MCP-1。HMGB 1还通过丝裂原活化蛋白激酶（MAPK）和磷酸肌醇-3-激酶（PI 3 K）途径诱导体外培养的大鼠肾小管上皮细胞分泌MCP-1。患有晶体诱导性肾炎的Hmgb 1 +/−小鼠显示肾脏和尿液中MCP-1表达减少，肾脏中巨噬细胞的数量显著减少。我们的结论是，HMGB 1是一种新的介质参与晶体诱导的肾炎，放大肉芽肿性炎症的循环中，MCP-1吸引活化的巨噬细胞，导致过度和持续的HMGB 1释放。HMGB 1可能成为抑制慢性肉芽肿性疾病的新靶点。
Granulomatous nephritis can be triggered by diverse factors and results in kidney failure. However, despite accumulating data about granulomatous inflammation, pathogenetic mechanisms in nephritis remain unclear. The DNA-binding high-mobility group box-1 protein (HMGB1) initiates and propagates inflammation when released by activated macrophages, functions as an “alarm cytokine” signaling tissue damage. In this study, we demonstrated elevated HMGB1 expression in renal granulomas in rats with crystal-induced granulomatous nephritis caused by feeding an adenine-rich diet. HMGB1 levels were also raised in urine and serum, as well as monocyte chemoattractant protein-1 (MCP-1), a mediator of granulomatous inflammation. Injection of HMGB1 worsened renal function and upregulated MCP-1 in rats with crystal-induced granulomatous nephritis. HMGB1 also induced MCP-1 secretion through mitogen-activated protein kinase (MAPK) and phosphoinositide-3-kinase (PI3K) pathways in rat renal tubular epithelial cells in vitro. Hmgb1+/− mice with crystal-induced nephritis displayed reduced MCP-1 expression in the kidneys and in urine and the number of macrophages in the kidneys was significantly decreased. We conclude that HMGB1 is a new mediator involved in crystal-induced nephritis that amplifies granulomatous inflammation in a cycle where MCP-1 attracts activated macrophages, resulting in excessive and sustained HMGB1 release. HMGB1 could be a novel target for inhibiting chronic granulomatous diseases.
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影响因子：
30.8
作者：
Calogero, S;Grassi, F;Bianchi, ME
通讯作者：
Bianchi, ME
DOI：
10.1165/rcmb.2002-0163oc
发表时间：
2003-07-01
影响因子：
6.4
作者：
Fenhalls, G;Squires, GR;Lukey, PT
通讯作者：
Lukey, PT
影响因子：
7
作者：
Heid, CA;Stevens, J;Williams, PM
通讯作者：
Williams, PM
影响因子：
4.4
作者：
Fan, Jie;Li, Yuehua;Wilson, Mark A.
通讯作者：
Wilson, Mark A.
影响因子：
5.5
作者：
Bell, Charles W.;Jiang, Weiwen;Pisetsky, David S.
通讯作者：
Pisetsky, David S.