Zhe Zhang1, Fang Wu, FenPing Zheng, Hong Li. 1. Department of Endocrinology, Affiliated Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, People's Republic of China.
Abstract
BACKGROUND/AIMS: Transforming growth factor beta(1) (TGF-beta(1)) is a key mediator in diabeticnephropathy (DN). Decorin, a natural inhibitor of TGF-beta(1), may have healing properties. We investigated whether overexpression of decorin in the kidneys of streptozocin (STZ)-induced diabetic rats improved pathogenic and clinical changes of DN. METHODS: Forty-eight Sprague-Dawley rats were evenly divided into 4 groups: STZ-induced diabetic rats (diabetic-control), decorin adenovirus vector (Ad)-treated STZ rats (Ad-decorin), and Ad-lacZ-treated STZ rats (Ad-lacZ), and vehicle control (PBS-control). At 10, 12, and 16 weeks after STZ treatment, we measured urinary albumin excretion (UAE), and immunolabeled type IV collagen in histological samples of rat kidney. We also measured kidney decorin and TGF-beta(1) levels by reverse transcription polymerase chain reaction and Western blot. Phosphorylated Smad2,3 (p-Smad2,3) was also measured by Western blot. RESULTS: Decorin gene transfection mediated by a recombinant adenovirus has antirenal fibrosis and anti-albuminuria effects in STZ-induced diabetic rats. TGF-beta(1) mRNA and protein expression in diabetic kidney were reduced 2 weeks after Ad-decorin injection. CONCLUSION: The renal protective effect of decorin in diabetic rats is at least partly due to the downregulation of the TGF-beta(1)/Smad signaling pathway. Ad-decorin shows potential as a therapeutic for human DN. Copyright 2010 S. Karger AG, Basel.
BACKGROUND/AIMS: Transforming growth factor beta(1) (TGF-beta(1)) is a key mediator in diabeticnephropathy (DN). Decorin, a natural inhibitor of TGF-beta(1), may have healing properties. We investigated whether overexpression of decorin in the kidneys of streptozocin (STZ)-induced diabeticrats improved pathogenic and clinical changes of DN. METHODS: Forty-eight Sprague-Dawley rats were evenly divided into 4 groups: STZ-induced diabeticrats (diabetic-control), decorin adenovirus vector (Ad)-treated STZrats (Ad-decorin), and Ad-lacZ-treated STZrats (Ad-lacZ), and vehicle control (PBS-control). At 10, 12, and 16 weeks after STZ treatment, we measured urinary albumin excretion (UAE), and immunolabeled type IV collagen in histological samples of rat kidney. We also measured kidney decorin and TGF-beta(1) levels by reverse transcription polymerase chain reaction and Western blot. Phosphorylated Smad2,3 (p-Smad2,3) was also measured by Western blot. RESULTS:Decorin gene transfection mediated by a recombinant adenovirus has antirenal fibrosis and anti-albuminuria effects in STZ-induced diabeticrats. TGF-beta(1) mRNA and protein expression in diabetic kidney were reduced 2 weeks after Ad-decorin injection. CONCLUSION: The renal protective effect of decorin in diabeticrats is at least partly due to the downregulation of the TGF-beta(1)/Smad signaling pathway. Ad-decorin shows potential as a therapeutic for human DN. Copyright 2010 S. Karger AG, Basel.
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