Renal Tubulointerstitial Fibrosis in OVE26 Type 1 Diabetic Mice
Renal Tubulointerstitial Fibrosis in OVE26 Type 1 Diabetic Mice
复制标题
DOI：
10.1159/000178763
复制
发表时间：
2009-01-01
影响因子：
--
通讯作者：
Klein, Jon B.
中科院分区：
文献类型：
--
作者：
Powell, David W.;Bertram, Clinton C.;Klein, Jon B.
背景/目的：肾小管间质纤维化(TIF)是进展性糖尿病肾病的显著特征。这项研究的目的是确定在转基因的OVE26 1型糖尿病小鼠中是否存在TIF的特征，并确定与TIF相关的信号事件。方法：采用免疫组织化学和免疫印迹方法检测TIF在OVE26糖尿病小鼠和正常小鼠肾脏中的表达。结果：TIF的病理特征是肌成纤维细胞聚集，细胞外基质在肾小管间质过度沉积。OVE26糖尿病大鼠肾脏小管间质肌成纤维细胞标志物(α-平滑肌肌动蛋白)、纤维连接蛋白和I型胶原染色增加。糖尿病肾小管中促纤维化细胞因子转化生长因子-β的含量也增加。由于损伤涉及上皮细胞-细胞接触的丧失促进组织纤维化，我们检测了黏附蛋白E-钙粘附素的表达。糖尿病大鼠肾脏E-钙粘素染色的肾小管百分率降低。转化生长因子-β信号的重要调节因子糖原合成酶-3(GSK-3)α和β也有差异表达。结论：这些结果表明转化生长因子-β诱导的TIF在OVE26糖尿病小鼠中发生，为定义糖尿病诱导的TIF的新的调节事件和治疗策略提供了一个实用的体内模型。版权所有(C)2009年S.Karger AG，巴塞尔
Background/Aims: Tubulointerstitial fibrosis (TIF) is a prominent feature of progressive diabetic nephropathy. The goal of this study was to determine if hallmarks of TIF occur in the transgenic OVE26 type 1 diabetic mouse and define signaling events associated with TIF. Methods: The expression patterns of several phenotypic markers of TIF were determined in kidneys of OVE26 diabetic and control mice by immunohistochemistry and immunoblot analysis. Results: Pathological signatures of TIF are an accumulation of myofibroblasts and excessive deposition of extracellular matrix in the tubulointerstitium. Kidneys from OVE26 diabetic animals exhibited an increase in tubulointerstitial myofibroblast marker (alpha-smooth muscle actin), fibronectin and collagen I staining. Abundance of the pro-fibrotic cytokine TGF-beta was also enhanced in diabetic tubules. As injury involving loss of epithelial cell-cell contact promotes tissue fibrosis, we examined expression of the adhesion protein, E-cadherin. The percent of E-cadherin-stained tubules was decreased in diabetic kidneys. Prominent regulators of TGF-beta signaling, glycogen synthase kinase-3 (GSK-3) alpha and beta, were also differentially expressed. Conclusions: These results indicate that TGF-beta-induced TIF occurs in OVE26 diabetic mice, providing a practical in vivo model for defining novel regulatory events and treatment strategies for diabetes-induced TIF. Copyright (c) 2009 S. Karger AG, Basel