Glomerular angiotensinogen protein is enhanced in pediatric IgA nephropathy
Glomerular angiotensinogen protein is enhanced in pediatric IgA nephropathy
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DOI：
10.1007/s00467-008-0801-6
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发表时间：
2008-08-01
影响因子：
3
通讯作者：
Kagami, Shoji
中科院分区：
文献类型：
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作者：
Takamatsu, Masanori;Urushihara, Maki;Kagami, Shoji
肾内肾素-血管紧张素系统（RAS）的增强与肾损伤的发生和发展有关。为了研究血管紧张素原（AGT）表达是否参与肾小球RAS活性和肾小球损伤，我们检测了来自免疫球蛋白A肾病（IgAN）（23）和轻微肾小球异常（MGA）（8）患者样本的肾小球AGT表达及其与其他RAS组分表达的相关性以及肾小球损伤水平。免疫组化结果显示，IgAN肾小球内皮细胞（GEC）和系膜细胞表达AGT蛋白，而MGA肾小球表达AGT蛋白。肾小球AGT蛋白水平与肾小球血管紧张素II（angII）、转化生长因子-β（TGF-β）、α-平滑肌肌动蛋白、肾小球细胞数和肾小球硬化评分水平密切相关，但与肾小球血管紧张素转换酶和angII 1型受体水平无关。实时聚合酶链反应（RT-PCR）和蛋白质印迹分析使用培养的人GEC表明，血管紧张素II上调AGT信使核糖核酸（mRNA）和蛋白质表达的剂量和时间依赖性的方式。这些数据表明，激活的肾小球AGT表达可能参与局部血管紧张素II产生的升高，从而可能导致IgAN中TGF-β产生增加和肾小球损伤的发展。血管紧张素II刺激增加GEC-AGT的产生可能会在正反馈回路中进一步驱动肾小球损伤。
Enhanced intrarenal renin-angiotensin system (RAS) is implicated in the development and progression of renal injury. To investigate whether angiotensinogen (AGT) expression is involved in glomerular RAS activity and glomerular injury, we examined glomerular AGT expression and its correlation with expression of other RAS components, and levels of glomerular injury in samples from patients with immunoglobulin A nephropathy (IgAN) (23) and minor glomerular abnormalities (MGA) (8). Immunohistochemistry showed that AGT protein was highly expressed by glomerular endothelial cells (GEC) and mesangial cells in nephritic glomeruli of IgAN compared with glomeruli of MGA. Levels of glomerular AGT protein were well correlated with levels of glomerular angiotensin II (ang II), transforming growth factor-beta (TGF-beta), alpha- smooth- muscle actin, glomerular cell number, and glomerulosclerosis score but not with those of glomerular angiotensin-converting enzyme and ang II type 1 receptor. Real-time polymerase chain reaction (RT-PCR) and Western blot analyses using cultured human GEC indicated that ang II upregulated AGT messenger ribonucleic acid ( mRNA) and protein expression in a dose- and time-dependent manner. These data suggest that activated glomerular AGT expression is likely involved in elevated local ang II production and, thereby, may contribute to increased TGF-beta production and development of glomerular injury in IgAN. Augmentation of GEC-AGT production with ang II stimulation might drive further glomerular injury in a positive-feedback loop.