Merchant Michael L, Klein Jon B
Kidney Disease Program, University of Louisville, Louisville, KY 40202, USA.
Semin Nephrol. 2007 Nov;27(6):627-36. doi: 10.1016/j.semnephrol.2007.09.003.
Proteomic methods have found broad applications in kidney disease research and more specifically in diabetic nephropathy (DN) research. Proteomic methods such as 2-dimensional gel electrophoresis have been used to gain insight into glomerular and tubular nephropathies including DN. At the protein level, differences in high-abundant proteins in DN have been shown to reflect primarily differentially posttranslationally modified plasma proteins. Higher-sensitivity proteomic methods (eg, liquid chromatography-mass spectrometry) have pushed the boundaries on the known urinary proteome to include more than 1,500 proteins. These same high-sensitivity methods have been applied toward profiling urinary peptides, which has resulted in methods to diagnostically screen urine to differentiate between type-2 diabetes mellitus and type-1 diabetes mellitus urine, normal versus microalbuminuria, or by angiotensin II receptor blocker treatment. Proteomic methods are being used to show response to insulin gene therapy in an animal model or alterations in the renal cortex mitochondrial proteome with the development of the diabetic phenotype. Proteomic methods continue to aid in the discovery of new mechanisms of diabetic pathology and understanding of the etiology of diabetic complications.
蛋白质组学方法在肾脏疾病研究,尤其是糖尿病肾病(DN)研究中得到了广泛应用。二维凝胶电泳等蛋白质组学方法已被用于深入了解包括DN在内的肾小球和肾小管肾病。在蛋白质水平上,DN中高丰度蛋白质的差异主要反映了翻译后修饰的血浆蛋白质的差异。更高灵敏度的蛋白质组学方法(如液相色谱-质谱联用)拓展了已知尿蛋白质组的范围,使其包含超过1500种蛋白质。这些同样高灵敏度的方法已应用于尿肽谱分析,从而产生了用于诊断性筛查尿液以区分2型糖尿病和1型糖尿病尿液、正常与微量白蛋白尿,或通过血管紧张素II受体阻滞剂治疗进行区分的方法。蛋白质组学方法正被用于展示动物模型中对胰岛素基因治疗的反应,或随着糖尿病表型的发展肾皮质线粒体蛋白质组的变化。蛋白质组学方法继续有助于发现糖尿病病理的新机制,并理解糖尿病并发症的病因。