Activation of the Smad pathway in glomeruli from a spontaneously diabetic rat model, OLETF rats

被引：9
作者：
Furuse, Y
Hashimoto, N
Maekawa, M
Toyama, Y
Nakao, A
Iwamoto, I
Sakurai, K
Suzuki, Y
Yagui, K
Yuasa, S
Toshimori, K
Saito, Y
机构：
[1] Asahi Gen Hosp, Dept Diabet & Metab Dis, Chiba 2892511, Japan
[2] Chiba Univ, Grad Sch Med, Dept Clin Cell Biol, Chiba, Japan
[3] Chiba Univ, Grad Sch Med, Dept Anat & Dev Biol, Chiba, Japan
[4] Univ Yamanashi, Fac Med, Dept Immunol, Yamanashi, Japan
[5] Matsudo Gen Hosp, Dept Internal Med, Chiba, Japan
[6] Natl Ctr Neurol & Psychiat, Natl Inst Neurosci, Dept Ultrastruct Res, Tokyo, Japan
来源：
NEPHRON EXPERIMENTAL NEPHROLOGY | 2004年 / 98卷 / 03期
关键词：
Smads; transforming growth factor-beta; OLETF; diabetic nephropathy; glomerulus;
D O I：
10.1159/000080685
中图分类号：
R5 [内科学]; R69 [泌尿科学（泌尿生殖系疾病）];
学科分类号：
1002 ; 100201 ;
摘要：
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. Methods: We evaluated the time course of TGF-beta(1) 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. Results: 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-beta(1) 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. Conclusions: 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. Copyright (C) 2004 S. Karger AG, Basel.
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页码：E100 / E108
页数：9
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