Peritubular ischemia contributes more to tubular damage than proteinuria in immune-mediated glomerulonephritis
Peritubular ischemia contributes more to tubular damage than proteinuria in immune-mediated glomerulonephritis
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DOI：
10.1681/asn.2007020226
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发表时间：
2008-02-01
影响因子：
13.6
通讯作者：
Tomino, Yasuhiko
中科院分区：
文献类型：
--
作者：
Wong, Muh Geot;Suzuki, Yusuke;Tomino, Yasuhiko
蛋白尿是肾小管间质损伤进展的关键因素。最近，由于管周毛细血管损失而导致的肾小管缺血已被确定为疾病进展的另一个主要因素，但这些损伤对肾小管间质损伤的相对贡献尚不清楚。在野生型（WT）和Fc受体敲除（FcRKO）小鼠中诱导抗肾小球基底膜肾小球肾炎，已显示其相对保护肾小球内皮损伤。尽管蛋白尿程度相当，但WT小鼠的肾功能明显比FcRKO小鼠差，沿着实时PCR和免疫组化显示I型胶原和肾损伤分子-1（急性肾小管损伤的敏感标志物）的表达更高。此外，与FcRKO小鼠相比，WT小鼠通过活体视频显微镜观察显示肾小管周围红细胞速度降低更大，组织缺氧显著增加。在体外，肾损伤分子-1的表达增加培养的小鼠近端肾小管上皮细胞在细胞应激反应，包括缺氧，饥饿，暴露于过量的蛋白质，因此，它表明，缺氧的侮辱更强烈地影响肾小管间质损伤比蛋白尿单独在亚急性肾脏疾病模型。
Proteinuria is a key factor in the progression of tubulointerstitial injury. Recently, tubular ischemia as a result of loss of peritubular capillaries has been identified as another major contributor to disease progression, but the relative contribution of these insults on tubulointerstitial damage is unknown. Anti-glomerular basement membrane glomerulonephritis was induced in wild-type (WT) and Fc receptor knockout (FcRKO) mice, which have been shown to be relatively protected against glomerular endothelial injury. Despite comparable degrees of proteinuria, WT mice developed significantly worse renal function than FcRKO mice, along with higher expression of both type I collagen and kidney injury molecule-1 (a sensitive marker of acute tubular injury) by real-time PCR and immunohistochemistry. In addition, compared with FcRKO mice, WT mice exhibited a greater decrease in peritubular red blood cell velocity by intravital videomicroscopy and a marked increase of tissue hypoxia. In vitro, kidney injury molecule-1 expression increased in cultured mouse proximal tubular epithelial cells in response to cellular stresses, including hypoxia, starvation, and exposure to excessive protein; therefore, it is suggested that hypoxic insults more strongly influence tubulointerstitial damage than proteinuria alone in models of subacute renal disease.