Smad7 gene transfer inhibits peritoneal fibrosis.
Fibrosis mediated by transforming growth factor-beta (TGF-beta) is a common cause of peritoneal dialysis (PD) failure. In a model of peritoneal fibrosis, we tested the effect of Smad7, an inhibitor of TGF-beta signaling, using an ultrasound-microbubble-mediated delivery system. Rats were given daily PD for 4 weeks and received Smad7 or control plasmid transfer. The ultrasound technique enhanced Smad7 expression in a dose-dependent manner in more than 80% of the peritoneal cells after 3 days. The expression decreased by 14 days, but this was corrected by a second gene transfer. The overexpression of Smad7 substantially inhibited Smad2/3 activation, TGF-beta, plasminogen activator inhibitor-1, extracellular matrix, and myofibroblast mRNA, and protein expression in the peritoneal cells. The decreased peritoneal injury included the rise of mass transfer of glucose, a reduction of the ultrafiltration rate, and fibrotic thickening. Our studies suggest that ultrasound-mediated Smad7 gene delivery may be useful in the prevention or treatment of dialysis-induced peritoneal fibrosis.
Nie
J
J
Department of Nephrology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
Dou
X
X
Hao
W
W
Wang
X
X
Peng
W
W
Jia
Z
Z
Chen
W
W
Li
X
X
Luo
N
N
Lan
H Y
HY
Yu
X Q
XQ
D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004848:Epithelium / Q000378:metabolism / Q000473:pathology; D005355:Fibrosis / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D018014:Gene Transfer Techniques; D008297:Male; D010530:Peritoneal Dialysis / Q000009:adverse effects; D010537:Peritoneum / Q000378:metabolism / Q000473:pathology*; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D051899:Smad2 Protein / Q000378:metabolism; D051906:Smad7 Protein / Q000235:genetics* / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism
D017395:Plasminogen Activator Inhibitor 1; D051899:Smad2 Protein; C497784:Smad2 protein, rat; D051906:Smad7 Protein; C497808:Smad7 protein, rat; D016212:Transforming Growth Factor beta