Department of Medicine and Clinical Science, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.
Nephrology (Carlton). 2010 Aug;15(5):568-74. doi: 10.1111/j.1440-1797.2010.01342.x.
Nestin, an intermediate filament originally identified as a marker of neural progenitor cells, is transiently expressed in endothelial cells and tubuloepithelial cells during kidney development. However, in adult kidneys, podocytes are the only cells that express nestin. In this study, we examined tubulointerstitial nestin expression in human glomerulonephritis.
Renal biopsy specimens obtained from 41 adult patients with immunoglobulin (Ig)A nephropathy were studied. Nestin expression was determined by immunohistochemical staining and estimated by digital image analysis. To identify the phenotype of nestin-positive cells, a double immunofluorescent study was performed for nestin and CD34 (a marker for endothelial cells) or alpha-smooth muscle actin (alpha-SMA, a marker for myofibroblasts).
In normal kidney, nestin expression was restricted to the podocytes and was not detected in tubular cells and tubulointerstitial cells. In contrast, increased nestin expression was observed at tubulointerstitial areas of IgA nephropathy. The degree of tubulointerstitial nestin expression was positively correlated with tubulointerstitial fibrosis (r = 0.546, P < 0.001). The double immunofluorescent study showed that most nestin-positive cells in the interstitium were co-stained with CD34 or alpha-SMA, suggesting that peritubular endothelial cells and tubulointerstitial myofibroblasts express nestin during the progression of tubulointerstitial injury. In addition, strong nestin expression was associated with deterioration of renal function.
Nestin expression is associated with tubulointerstitial injury and predicts renal prognosis in IgA nephropathy. Nestin could be a new marker for peritubular endothelial cell injury and tubulointerstitial fibrosis.
巢蛋白最初被鉴定为神经祖细胞的标志物,是一种中间丝蛋白,在肾脏发育过程中短暂表达于内皮细胞和小管上皮细胞。然而,在成人肾脏中,足细胞是唯一表达巢蛋白的细胞。在本研究中,我们检测了人肾小球肾炎中肾小管间质巢蛋白的表达。
研究了 41 例成人免疫球蛋白(Ig)A 肾病患者的肾活检标本。通过免疫组织化学染色检测巢蛋白表达,并通过数字图像分析进行定量评估。为了鉴定巢蛋白阳性细胞的表型,进行了巢蛋白和 CD34(内皮细胞标志物)或α-平滑肌肌动蛋白(α-SMA,肌成纤维细胞标志物)的双重免疫荧光研究。
在正常肾脏中,巢蛋白表达局限于足细胞,而在肾小管细胞和肾小管间质细胞中未检测到。相反,在 IgA 肾病的肾小管间质区域观察到巢蛋白表达增加。肾小管间质巢蛋白表达程度与肾小管间质纤维化呈正相关(r=0.546,P<0.001)。双重免疫荧光研究显示,间质中大多数巢蛋白阳性细胞与 CD34 或 α-SMA 共染色,提示在肾小管间质损伤进展过程中,管周内皮细胞和肾小管间质肌成纤维细胞表达巢蛋白。此外,强烈的巢蛋白表达与肾功能恶化相关。
巢蛋白表达与肾小管间质损伤相关,并预测 IgA 肾病的肾脏预后。巢蛋白可能是管周内皮细胞损伤和肾小管间质纤维化的新标志物。