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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Am+J+Physiol+Renal+Physiol
2014 ; 307
(7
): F777-82
Nephropedia Template TP
Chaudhary K
; Moore H
; Tandon A
; Gupta S
; Khanna R
; Mohan RR
Am J Physiol Renal Physiol
2014[Oct]; 307
(7
): F777-82
PMID25056353
show ga
Peritoneal dialysis (PD) is a life-sustaining therapy for end-stage renal disease
(ESRD), used by 10-15% of the dialysis population worldwide. Peritoneal fibrosis
(PF) is a known complication of long-term PD and frequently follows episodes of
peritonitis, rendering the peritoneal membrane inadequate for dialysis.
Transforming growth factor (TGF)-? is an inducer of fibrosis in several tissues
and organs, and its overexpression has been correlated with PF. Animal models of
peritonitis have shown an increase in expression of TGF-? in the peritoneal
tissue. Decorin, a proteoglycan and component of the extracellular matrix,
inactivates TGF-?, consequently reducing fibrosis in many tissues. Recently, gold
nanoparticles (GNP) have been used for drug delivery in a variety of settings. In
the present study, we tested the possibility that GNP-delivered decorin gene
therapy ameliorates zymosan-mediated PF. We created a PF model using
zymosan-induced peritonitis. Rats were treated with no decorin, GNP-decorin, or
adeno-associated virus-decorin (AAV-decorin) and compared with controls. Tissue
samples were then stained for Masson's trichrome, enface silver, and hematoxylin
and eosin, and immunohistochemistry was carried out with antibodies to TGF-?1,
?-smooth muscle actin (?-SMA), and VEGF. Animals which were treated with
GNP-decorin and AAV-decorin gene therapy had significant reductions in PF
compared with untreated animals. Compared with untreated animals, the treated
animals had better preserved peritoneal mesothelial cell size, a significant
decrease in peritoneal thickness, and decreased ?-SMA. Quantitative PCR
measurements showed a significant decrease in the peritoneal tissue levels of
?-SMA, TGF-?, and VEGF in treated vs. untreated animals. This study shows that
both GNP-delivered and AAV-mediated decorin gene therapies significantly decrease
PF in vivo in a rodent model. This approach has important clinical translational
potential in providing a therapeutic strategy to prevent PF in PD patients.
|*Genetic Therapy
[MESH]
|*Rats, Sprague-Dawley
[MESH]
|Adenoviridae
[MESH]
|Animals
[MESH]
|Decorin/*genetics
[MESH]
|Gene Transfer Techniques
[MESH]
|Nanoparticles
[MESH]
|Peritoneal Fibrosis/chemically induced/*prevention & control
[MESH]