Effect of losartan on the glomerular protein expression profile of type 2 diabetic KKAy mice
Effect of losartan on the glomerular protein expression profile of type 2 diabetic KKAy mice
复制标题
氯沙坦对2型糖尿病KKAy小鼠肾小球蛋白表达谱的影响
DOI：
10.5301/jn.5000176
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发表时间：
2013-05-01
影响因子：
3.4
通讯作者：
Wang, Li-Ning
中科院分区：
文献类型：
--
作者：
Fan, Qiu-Ling;Yang, Gang;Wang, Li-Ning
背景资料：为探讨糖尿病肾病（DN）的发病机制并寻找新的治疗靶点，采用双向差异凝胶电泳（2D-DIGE）技术，对氯沙坦治疗后的KKAy小鼠肾小球蛋白表达谱进行分析。治疗12周后，用磁珠腹腔灌注法分离肾小球，提取肾小球蛋白。采用2D-DIGE和MALDI-TOF质谱分析肾小球蛋白表达谱。结果：氯沙坦治疗后，KKAy小鼠蛋白尿明显减少，肾脏病理损害明显减轻。在KKAy氯沙坦治疗小鼠和KKAy非治疗小鼠之间，总共有62种肾小球蛋白质差异表达。其中，28个蛋白表达上调，包括甘油激酶，亚硫酸氧化酶，甘氨酸脒基转移酶，腺苷高半胱氨酸酶。13个蛋白表达下调，包括3-巯基丙酮酸硫转移酶、ATP合成酶亚基d、60 kDa热休克蛋白和75 kDa葡萄糖调节蛋白（GRP 75）。共发现6种蛋白质在KKAy未治疗小鼠和C57 BL/6小鼠肾小球之间差异表达，并且它们的差异表达被氯沙坦治疗抑制，包括线粒体！结论：氯沙坦治疗可抑制线粒体的差异表达。ATP合成酶亚基d、GRP 75、硒结合蛋白1等在糖尿病KKAy小鼠肾小球中可能通过减少肾小球线粒体ROS的产生和抑制氧化应激而发挥肾脏保护作用。
Background: To investigate the pathogenesis of diabetic nephropathy (DN) and to search for novel therapeutic targets, the glomerular protein expression profile of KKAy mice treated by losartan was analyzed by two-dimensional differential gel electrophoresis (2D-DIGE).Methods: The eight-week-old KKAy mice were divided into the losartan treatment group and the non-treatment group, and C57BL/6 mice were used as the control group. After 12 weeks treatment, glomeruli were isolated by abdominal perfusion with magnetic beads, and the glomerular proteins were extracted. The glomerular protein expression profiles were investigated using 2D-DIGE and MALDI-TOF mass spectrometry. Western blot analysis was used to confirm the results of proteomics.Results: Losartan treatment improved albuminuria and renal pathologic lesion of KKAy mice. A total of 62 glomerular proteins were differentially expressed between the KKAy losartan treatment mice and KKAy non-treatment mice. Among them, the expression of 28 proteins were up-regulated, including glycerokinase, sulfite oxidase, glycine amidinotransferase, and adenosylhomocysteinase. The expression of 13 proteins were down-regulated, including 3-mercaptopyruvate sulfurtransferase, ATP synthase subunit d, 60 kDa heat shock protein, and 75 kDa glucose-regulated protein(GRP75). A total of six proteins were found to be differentially expressed between the KKAy non-treatment mice and C57BL/6 mice glomeruli, and their differential expression was suppressed by losartan treatment, including mitochondria! ATP synthase subunit d, GRP75, and selenium-binding protein 1 et al.Conclusions: Treatment with losartan suppresses the differential expression of mitochondria! ATP synthase subunit d, GRP75, selenium-binding protein 1 etc. In diabetic KKAy mice glomeruli, may play a renoprotective role by reducing glomerular mitochondrial ROS genesis and inhibiting oxidative stress.