Multiphoton Imaging of the Glomerular Permeability of Angiotensinogen
Multiphoton Imaging of the Glomerular Permeability of Angiotensinogen
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DOI：
10.1681/asn.2012010078
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发表时间：
2012-11-01
影响因子：
13.6
通讯作者：
Peti-Peterdi, Janos
中科院分区：
文献类型：
--
作者：
Nakano, Daisuke;Kobori, Hiroyuki;Peti-Peterdi, Janos
肾损伤患者和动物的尿中血管紧张素原排泄量增加。虽然血管紧张素原的肾小管合成增加是导致排泄增加的原因之一，但我们不知道系统性血管紧张素原的肾小球滤过，尤其是通过异常的肾小球滤过屏障，在多大程度上促进了尿量的增加。在这里，我们使用多光子显微镜来可视化和定量血管紧张素原在完整的小鼠和大鼠肾脏中的肾小球通透性。在健康小鼠和肾小球硬化早期的Munich-Wistar-Fromter大鼠中，系统输注Atto565标记的人血管紧张素原(Atto565-Hagt)的肾小球筛选系数仅为肾小球白蛋白筛选系数的25%，且尿液中检测不到它的存在。在肾脏疾病的晚期，Atto565-Hagt的肾小球通透性略高，但仍然非常低。此外，与尿白蛋白不同，内源性大鼠血管紧张素原的显著较高排泄量与Atto565-HAGT或Atto565-白蛋白肾小球筛选系数无关。这些结果有力地表明，绝大多数尿血管紧张素原来自肾小管而不是肾小球滤过。
Patients and animals with renal injury exhibit increased urinary excretion of angiotensinogen. Although increased tubular synthesis of angiotensinogen contributes to the increased excretion, we do not know to what degree glomerular filtration of systemic angiotensinogen, especially through an abnormal glomerular filtration barrier, contributes to the increase in urinary levels. Here, we used multiphoton microscopy to visualize and quantify the glomerular permeability of angiotensinogen in the intact mouse and rat kidney. In healthy mice and Munich-Wistar-Fromter rats at the early stage of glomerulosclerosis, the glomerular sieving coefficient of systemically infused Atto565-labeled human angiotensinogen (Atto565-hAGT), which rodent renin cannot cleave, was only 25% of the glomerular sieving coefficient of albumin, and its urinary excretion was undetectable. In a more advanced phase of kidney disease, the glomerular permeability of Atto565-hAGT was slightly higher but still very low. Furthermore, unlike urinary albumin, the significantly higher urinary excretion of endogenous rat angiotensinogen did not correlate with either the Atto565-hAGT or Atto565-albumin glomerular sieving coefficients. These results strongly suggest that the vast majority of urinary angiotensinogen originates from the tubules rather than glomerular filtration.