TNF-mediated damage to glomerular endothelium is an important determinant of acute kidney injury in sepsis.
TNF-mediated damage to glomerular endothelium is an important determinant of acute kidney injury in sepsis.
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DOI：
10.1038/ki.2013.286
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发表时间：
2014-01
影响因子：
19.6
通讯作者：
中科院分区：
文献类型：
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严重脓毒症常伴有急性肾损伤（AKI）和蛋白尿。在这里，我们研究了与脂多糖（LPS）处理相关的小鼠AKI和蛋白尿是否反映了肾小球内皮及其相关内皮表面层的损伤。LPS处理降低了内皮表层硫酸肝素蛋白聚糖和唾液酸的丰度，导致蛋白尿可能反映了肾小球滤过物选择性的改变。LPS处理降低肾小球滤过率（GFR），同时也引起肾小球内皮细胞超微结构的显著改变。lps组肾小球内皮细胞窗密度比对照组低5倍，平均窗直径比对照组高3倍。在TNF受体1 （TNFR1）敲除小鼠中，LPS对肾小球内皮表面层、内皮细胞窗、GFR和蛋白尿的影响减弱，表明这些LPS作用是由TNF-α激活TNFR1介导的。的确，静脉给药TNF可降低GFR，导致肾小球内皮细胞窗孔的丧失、窗孔直径的增加和肾小球内皮表层的损伤。LPS处理降低了肾脏血管内皮生长因子（VEGF）的表达。因此，我们的研究结果证实了肾小球内皮损伤（可能通过VEGF水平降低）在小鼠LPS脓毒症模型中AKI和蛋白尿的发生和进展中的重要作用。
Severe sepsis is often accompanied by acute kidney injury (AKI) and albuminuria. Here we studied whether the AKI and albuminuria associated with lipopolysaccharide (LPS) treatment in mice reflects impairment of the glomerular endothelium with its associated endothelial surface layer. LPS treatment decreased the abundance of endothelial surface layer heparan sulfate proteoglycans and sialic acid, and led to albuminuria likely reflecting altered glomerular filtration perm-selectivity. LPS treatment decreased the glomerular filtration rate (GFR), while also causing significant ultrastructural alterations in the glomerular endothelium. The density of glomerular endothelial cell fenestrae was 5-fold lower whereas the average fenestrae diameter was 3-fold higher in LPS-treated than in control mice. The effects of LPS on the glomerular endothelial surface layer, endothelial cell fenestrae, GFR, and albuminuria were diminished in TNF receptor 1 (TNFR1) knockout mice, suggesting that these LPS effects are mediated by TNF-α activation of TNFR1. Indeed, intravenous administration of TNF decreased GFR and led to loss of glomerular endothelial cell fenestrae, increased fenestrae diameter, and damage to the glomerular endothelial surface layer. LPS treatment decreased kidney expression of vascular endothelial growth factor (VEGF). Thus, our findings confirm the important role of glomerular endothelial injury, possibly by a decreased VEGF level, in the development and progression of AKI and albuminuria in the LPS model of sepsis in the mouse.
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影响因子：
--
作者：
Eremina, Vera;Baelde, Hans J.;Quaggin, Susan E.
通讯作者：
Quaggin, Susan E.
影响因子：
--
作者：
CURRY, FE;RUTLEDGE, JC;LENZ, JF
通讯作者：
LENZ, JF
影响因子：
7.8
作者：
Albelda, S M;Muller, W A;Buck, C A;Newman, P J
通讯作者：
Newman, P J
克隆哺乳动物肝素酶--肿瘤侵袭和转移过程中的一种重要酶
影响因子：
82.9
作者：
Hulett, MD;Freeman, C;Parish, CR
通讯作者：
Parish, CR
DOI：
10.1111/j.1748-1716.1993.tb09466.x
发表时间：
1993-01-01
期刊：
ACTA PHYSIOLOGICA SCANDINAVICA
影响因子：
--
作者：
JOHNSSON, E;HARALDSSON, B
通讯作者：
HARALDSSON, B