Nakatani Shinya, Kakehashi Anna, Ishimura Eiji, Yamano Shotaro, Mori Katsuhito, Wei Min, Inaba Masaaki, Wanibuchi Hideki
Department of Pathology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585, Japan.
Exp Diabetes Res. 2011;2011:979354. doi: 10.1155/2011/979354. Epub 2011 Oct 5.
To evaluate proteins associated with the development of diabetic nephropathy, a major cause of the end-stage renal disease, we analyzed protein expression in isolated glomeruli from spontaneous type 2 diabetic (OLETF) rats and their age-matched control littermates (LETO) in the early and proteinuric stages of diabetic nephropathy using QSTAR Elite LC-MS/MS. Among the 191 and 218 proteins that were altered significantly in the OLETF rats, twenty-four were actin cytoskeleton-associated proteins implicated in the formation of stress fibers, and the impairment of actin polymerization, intermediate filaments and microtubules. Importantly, sorbin and SH3 domain containing 2 (SORBS2), which is involved in the formation of stress fibers, was significantly upregulated in both stages of diabetic nephropathy (1.49- and 1.97-fold, resp.). Immunohistochemical and quantitative-PCR analyses revealed upregulation of SORBS2 in podocytes of glomeruli of OLETF rats. Our findings suggested that SORBS2 may be associated with the development of diabetic nephropathy possibility by reorganization of actin filaments.
为了评估与终末期肾病的主要病因——糖尿病肾病发展相关的蛋白质，我们使用QSTAR Elite液相色谱-串联质谱法，分析了自发性2型糖尿病（OLETF）大鼠及其年龄匹配的对照同窝仔鼠（LETO）在糖尿病肾病早期和蛋白尿期分离肾小球中的蛋白质表达。在OLETF大鼠中显著改变的191种和218种蛋白质中，有24种是与应力纤维形成、肌动蛋白聚合受损、中间丝和微管相关的肌动蛋白细胞骨架相关蛋白。重要的是，参与应力纤维形成的含sorbin和SH3结构域蛋白2（SORBS2）在糖尿病肾病的两个阶段均显著上调（分别为1.49倍和1.97倍）。免疫组织化学和定量PCR分析显示，OLETF大鼠肾小球足细胞中SORBS2上调。我们的研究结果表明，SORBS2可能通过肌动蛋白丝的重组与糖尿病肾病的发展相关。
