Anti-Inflammatory and Renal Protective Actions of Stanniocalcin-1 in a Model of Anti-Glomerular Basement Membrane Glomerulonephritis
Anti-Inflammatory and Renal Protective Actions of Stanniocalcin-1 in a Model of Anti-Glomerular Basement Membrane Glomerulonephritis
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DOI：
10.2353/ajpath.2009.080476
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发表时间：
2009-04-01
影响因子：
6
通讯作者：
Sheikh-Hamad, David
中科院分区：
文献类型：
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作者：
Huang, Luping;Garcia, Gabriela;Sheikh-Hamad, David
我们以前已经表明，斯钙素-1（STC 1）抑制巨噬细胞和T细胞的跨内皮迁移，抑制超氧化物生成的巨噬细胞，并减弱巨噬细胞对化学引诱剂的反应。为了研究STC 1对炎症的影响，在这项研究中，我们在STC 1转基因小鼠中诱导了巨噬细胞和T细胞介导的抗肾小球基底膜疾病模型，该模型显示血清STC 1水平升高，并优先在内皮细胞和巨噬细胞中表达STC 1。我们在基线和抗肾小球基底膜抗体治疗后检查了以下参数：血压; C-3a水平;尿量;蛋白尿;血尿素氮;肾脏C-3沉积、纤维化、组织学变化、细胞因子表达以及T细胞和巨噬细胞数量。与野生型小鼠相比，在抗肾小球基底膜处理后，STC 1转基因小鼠表现出：i）肾小球中炎性巨噬细胞浸润减少; ii）新月体形成和肾小球硬化显著减少; iii）间质纤维化减少; iv）肾功能保留和血压降低; v）肾小球中C3沉积减少;和vi）肾中巨噬细胞抑制蛋白-2和转化生长因子-β 2的表达降低。与基线相比，野生型小鼠，而不是STC 1转基因小鼠，有较高的蛋白尿和尿量显着减少。然而，STC 1对肾小球和肾小球中的T细胞数量以及TH 1或TH 2活化的细胞因子表达特征的影响最小。这些数据表明STC 1是一种有效的抗炎和肾脏保护蛋白。(Am J Pathol 2009，174：1368-1378; DOI：10.2353/ajpath.2009.080476）
We have previously shown that stanniocalcin-1 (STC1) inhibits the transendothelial migration of macrophages and T cells, suppresses superoxide generation in macrophages, and attenuates macrophage responses to chemoattractants. To study the effects of STC1 on inflammation, in this study we induced a macrophage- and T-cell-mediated model of anti-glomerular basement membrane disease in STC1 transgenic mice, which display elevated serum STC1 levels and preferentially express STC1 in both endothelial cells and macrophages. We examined the following parameters both at baseline and after anti-glomerular basement membrane antibody treatment: blood pressure; C-3a levels; urine output; proteinuria; blood urea nitrogen; and kidney C-3 deposition, fibrosis, histological changes, cytokine expression, and number of T cells and macrophages. Compared with wild-type mice, after anti-glomerular basement membrane treatment STC1 transgenic mice exhibited: i) diminished infiltration of inflammatory macrophages in the glomeruli; ii) marked reduction in crescent formation and sclerotic glomeruli; iii) decreased interstitial fibrosis; iv) preservation of kidney function and lower blood pressure; v) diminished C3 deposition in the glomeruli; and vi) reduced expression of macrophage inhibitory protein-2 and transforming growth factor-beta 2 in the kidney. Compared with baseline, wild-type mice, but not STC1 transgenic mice, had higher proteinuria and a marked reduction in urine output. STC1 had minimal effects, however, on both T-cell number in the glomeruli and interstitium and on cytokine expression characteristic of either TH1 or TH2 activation. These data suggest that STC1 is a potent anti-inflammatory and renal protective protein. (Am J Pathol 2009, 174:1368-1378; DOI: 10.2353/ajpath.2009.080476)