Division of Nephrology and Metabolism, Department of Internal Medicine, School of Medicine, Tokai University, Isehara, Kanagawa, Japan.
J Nephrol. 2012 Mar-Apr;25(2):233-9. doi: 10.5301/JN.2011.8449.
Tubulointerstitial fibrosis (TIF) is seen as the final stage of progressive nephropathy, and the degree of TIF is reported to be a major determinant in renal outcomes. In recent years, epithelial-mesenchymal transition (EMT) and the zinc-finger transcription factor snail homolog 1 (Snai1) have each been implicated in the mechanism of TIF. The relationship between EMT and these transcription factors is unclear, however, so in this study we attempted to elucidate the correlation between the expression of Snai1 and clinical markers.
We performed immunohistochemical staining on human renal tissue obtained from patients with diabetic nephropathy (DN), IgA nephropathy (IgAN), minimal change disease (MCD) and minor glomerular abnormality (MGA) using anti-Snai1 and anti-vimentin antibodies. We counted Snai1-positive and Snai1/vimentin double positive tubular epithelial cells.
Snai1 protein was mainly observed in the nuclei of flattened, damaged tubular epithelial cells, especially in IgAN and DN, and positive cell numbers were significantly higher in IgAN than in MGA, MCD or DN. Snai1/vimentin double staining showed that some vimentin-positive tubular epithelial cells also contained Snai1-positive nuclei, and double positive cell numbers were increased in IgAN and DN. Statistical analysis revealed positive correlations between Snai1/vimentin double positive cell numbers and proteinuria and creatinine in IgAN. Positive correlations were also seen between Snai1/vimentin double positive cell numbers and the severity of proteinuria in DN.
The results of this study indicate that Snai1 plays an important role in TIF in patients with progressive nephropathy.
肾小管间质纤维化（TIF）被视为进行性肾病的终末阶段，TIF 的程度据报道是决定肾脏预后的主要因素。近年来，上皮-间充质转化（EMT）和锌指转录因子 snail 同源物 1（Snai1）都被认为与 TIF 的发生机制有关。然而，EMT 与这些转录因子之间的关系尚不清楚，因此本研究试图阐明 Snai1 表达与临床标志物之间的相关性。
我们使用抗 Snai1 和抗波形蛋白抗体对来自糖尿病肾病（DN）、IgA 肾病（IgAN）、微小病变性肾病（MCD）和轻微肾小球异常（MGA）患者的人肾组织进行免疫组织化学染色。我们计数了 Snai1 阳性和 Snai1/波形蛋白双阳性肾小管上皮细胞。
Snai1 蛋白主要在扁平、受损的肾小管上皮细胞的核中观察到，尤其是在 IgAN 和 DN 中，IgAN 中的阳性细胞数明显高于 MGA、MCD 或 DN。Snai1/波形蛋白双重染色显示，一些波形蛋白阳性的肾小管上皮细胞也含有 Snai1 阳性核，并且在 IgAN 和 DN 中双阳性细胞数增加。统计分析显示，在 IgAN 中，Snai1/波形蛋白双阳性细胞数与蛋白尿和肌酐呈正相关。在 DN 中，Snai1/波形蛋白双阳性细胞数与蛋白尿严重程度也呈正相关。
本研究结果表明，Snai1 在进行性肾病患者的 TIF 中发挥重要作用。
