Furuse Yoko, Hashimoto Naotake, Maekawa Mamiko, Toyama Yoshiro, Nakao Atsuhito, Iwamoto Itsuo, Sakurai Kenichi, Suzuki Yoshifumi, Yagui Kazuo, Yuasa Shigeki, Toshimori Kiyotaka, Saito Yasushi
Department of Clinical Cell Biology, Graduate School of Medicine, Chiba University, Chiba, Japan.
Nephron Exp Nephrol. 2004;98(3):e100-8. doi: 10.1159/000080685.
BACKGROUND/AIMS: Transforming growth factor-beta (TGF-beta) mediates the excess accumulation of extracellular matrix in the diabetic kidney. Smad family proteins have been identified as signal transducers for the TGF-beta superfamily. We sought to characterize the role of Smad proteins in mediating TGF-beta responses in the development of diabetic nephropathy.
We evaluated the time course of TGF-beta1 fibronectin, Smad2 and Smad3 protein expression and Smad3 activation in glomeruli from spontaneously diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats, using immunohistochemistry and Western blot analysis.
The glomeruli of diabetic OLETF rats showed not only accelerated activation of Smad3, but also enhanced protein expression of Smad2 and Smad3, which occurred in parallel to the increased expression of TGF-beta and fibronectin compared with glomeruli of control, Long-Evans Tokushima Otsuka (LETO) rats at 30 weeks of age. No differences were found in TGF-beta1 fibronectin, Smad2 and Smad3 protein expression and Smad3 activation in glomeruli between the two strains at 12 weeks of age when OLETF rats were not diabetic.
The enhancement of Smad protein expression and activation may be involved in the TGF-beta signaling cascade that plays an important role in the development of diabetic nephropathy through progressive expansion of the mesangial matrix.
背景/目的：转化生长因子-β（TGF-β）介导糖尿病肾病中细胞外基质的过度积聚。Smad家族蛋白已被确定为TGF-β超家族的信号转导分子。我们试图阐明Smad蛋白在糖尿病肾病发展过程中介导TGF-β反应的作用。
我们采用免疫组织化学和蛋白质印迹分析，评估了自发性糖尿病大耳白兔（OLETF）大鼠肾小球中TGF-β1、纤连蛋白、Smad2和Smad3蛋白表达以及Smad3激活的时间进程。
与30周龄对照的大耳白兔（LETO）大鼠肾小球相比，糖尿病OLETF大鼠的肾小球不仅显示Smad3激活加速，而且Smad2和Smad3蛋白表达增强，这与TGF-β和纤连蛋白表达增加同时出现。在12周龄OLETF大鼠未患糖尿病时，两品系大鼠肾小球中TGF-β1、纤连蛋白、Smad2和Smad3蛋白表达以及Smad3激活未发现差异。
Smad蛋白表达和激活的增强可能参与了TGF-β信号级联反应，该反应通过系膜基质的逐渐扩张在糖尿病肾病的发展中起重要作用。
