Essawy M, Soylemezoglu O, Muchaneta-Kubara E C, Shortland J, Brown C B, el Nahas A M
Sheffield Kidney Institute, Northern General Hospital Trust, UK.
Nephrol Dial Transplant. 1997 Jan;12(1):43-50. doi: 10.1093/ndt/12.1.43.
The cellular mediators of progressive renal fibrosis in diabetic nephropathy remain unknown. Myofibroblasts have been implicated in the pathogenesis of experimental and clinical renal fibrosis. Their role in the progression of diabetic nephropathy is the subject of this study.
We have studied by immuno-histochemistry the expression of cytoskeletal proteins associated with the activation of myofibroblasts; alpha-smooth-muscle actin (alpha-SMA), vimentin (Vi) and desmin (D), in the kidneys of 25 patients with diabetic nephropathy (5 patients had a superimposed glomerulonephritis). Comparisons were made with normal tissue from three kidneys removed for renal-cell carcinoma. Correlations were studied between clinical and biochemical parameters with the expression of renal cytoskeletal proteins.
In normal kidneys, cells expressing alpha-SMA were confined to the vascular media and adventitia while immunoreactive Vi was detected in glomerular epithelial cells. In diabetic kidneys, cells expressing alpha-SMA were detected primarily in the renal interstitium and to a lesser extent in some glomeruli in association with mesangial proliferation. Vimentin immunostain decreased in glomeruli displaying diabetic hyalinosis and sclerosis. By contrast, strong Vi immunoreactivity was noted in atrophic diabetic tubules and to a lesser extent in the interstitium. Desmin was not detected in either normal or diabetic kidneys. Close correlations were observed between the expression of renal cytoskeletal proteins and the progression of renal insufficiency. Interstitial alpha-SMA proved to be a predictor of progressive diabetic nephropathy (R2 for 1/serum Cr slope = 0.608, P = 0.00001). This predictive value was superior to, and independent from, that of the best conventional histological predictive parameters; tubular atrophy (R2 = 0.477, P = 0.00004) and interstitial fibrosis (R2 = 0.28, P = 0.001).
We have demonstrated in this study the neoexpression of cytoskeletal proteins within diabetic kidneys. This has allowed the identification of new predicting histological markers for the progression of diabetic nephropathy.
糖尿病肾病中进行性肾纤维化的细胞介质尚不清楚。肌成纤维细胞与实验性和临床肾纤维化的发病机制有关。它们在糖尿病肾病进展中的作用是本研究的主题。
我们通过免疫组织化学研究了25例糖尿病肾病患者（5例合并肾小球肾炎）肾脏中与肌成纤维细胞活化相关的细胞骨架蛋白α-平滑肌肌动蛋白（α-SMA）、波形蛋白（Vi）和结蛋白（D）的表达。与因肾细胞癌切除的三个肾脏的正常组织进行了比较。研究了临床和生化参数与肾细胞骨架蛋白表达之间的相关性。
在正常肾脏中，表达α-SMA的细胞局限于血管中层和外膜，而在肾小球上皮细胞中检测到免疫反应性Vi。在糖尿病肾脏中，表达α-SMA的细胞主要在肾间质中检测到，在一些与系膜增生相关的肾小球中较少。在显示糖尿病玻璃样变性和硬化的肾小球中，波形蛋白免疫染色减少。相比之下，在萎缩的糖尿病肾小管中观察到强烈的Vi免疫反应性，在间质中较少。在正常或糖尿病肾脏中均未检测到结蛋白。观察到肾细胞骨架蛋白的表达与肾功能不全的进展密切相关。间质α-SMA被证明是进行性糖尿病肾病的预测指标（1/血清肌酐斜率的R2 = 0.608，P = 0.00001）。这种预测价值优于并独立于最佳传统组织学预测参数；肾小管萎缩（R2 = 0.477，P = 0.00004）和间质纤维化（R2 = 0.28，P = 0.001）。
我们在本研究中证明了糖尿病肾脏中细胞骨架蛋白的新表达。这使得能够识别糖尿病肾病进展的新的预测性组织学标志物。
