Adenovirus-mediated decorin gene transfection has therapeutic effects in a streptozocin-induced diabetic rat model.
OBJECTIVE
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.


CONCLUSIONS
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.
Zhang
Zhe
Z
Department of Endocrinology, Affiliated Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, People's Republic of China.
Wu
Fang
F
Zheng
FenPing
F
Li
Hong
H
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D058575:Decorin / Q000235:genetics* / Q000627:therapeutic use*; D003921:Diabetes Mellitus, Experimental / Q000628:therapy*; D003928:Diabetic Nephropathies / Q000188:drug therapy; D005260:Female; D005822:Genetic Vectors; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000378:metabolism
D058575:Decorin; D016212:Transforming Growth Factor beta