Korean J Nephrol.  2008 Jul;27(4):421-432.

The Effect of Adenoviral-mediated Gene Transfer of Bone Morphogenic Protein-7 on Peritoneal Fibrosis in an Animal Model of Peritoneal Dialysis

• Choi JY
• Jin MK
• Chun JH
• Hyun SH
• Choi HJ
• Choi HJ
• Cho JH
• Kim MH
• Ryu HM
• Oh EJ
• Choi SY
• Kim CD
• Kim YL
• Park SH

Abstract

PURPOSE: TGF-beta-induced epithelial-mesenchymal transition (EMT) is associated with peritoneal fibrosis during PD. We conducted this study to evaluate the effect of BMP-7 adenoviral gene transfer on the functional and structural changes of peritoneum and whether it is associated with peritoneal EMT using an animal PD model.
METHODS
Forty Sprague-Dawley rats were divided into five groups; Control (C, n=8), Dialysis (D, n= 8), Rest (R, n=8), BMP-7 (B, n=8) and LacZ (L, n=8) group. Peritoneal function was assessed on baseline, 3rd, 6th, 8th weeks after PD. Immunohistochemistry for TGF-beta, VEGF, laminin and aquaporin-1 was performed in addition to morphometric analysis of peritoneum. Immunofluorescence staining with western blotting for alpha-SMA and E-cadherin, as markers of EMT, was performed.
RESULTS
The thickness of submesothelial matrix was highest in D and significantly decreased in B compared to D, R and L. D/D0 glucose at 8 weeks was significantly increased in B and L compared to that of at 6 weeks, but there were no significant differences among R, B and L at 8 weeks. TGF-beta1 and VEGF expression was observed in submesothelial matrix in D and decreased in R, B and L. Peritoneal fibrosis and functional deterioration of peritoneal membrane were associated with EMT, which was partially reversed in R, B and L.
CONCLUSIONS
BMP-7 gene transfer to peritoneum was not associated with the additive therapeutic effect on peritoneal function compared to the peritoneal rest, although it improved morphologic changes of peritoneum.

Keyword

Gene therapy; Bone morphogenetic protein 7; Transforming growth factor-beta; Peritoneal dialysis

MeSH Terms

Animals
Blotting, Western
Bone Morphogenetic Protein 7
Cadherins
Dialysis
Epithelial-Mesenchymal Transition
Fluorescent Antibody Technique
Genetic Therapy
Glucose
Immunohistochemistry
Laminin
Membranes
Models, Animal
Peritoneal Dialysis
Peritoneal Fibrosis
Peritoneum
Rats, Sprague-Dawley
Transforming Growth Factor beta
Transforming Growth Factor beta1
Vascular Endothelial Growth Factor A
Bone Morphogenetic Protein 7
Cadherins
Glucose
Laminin
Transforming Growth Factor beta
Transforming Growth Factor beta1
Vascular Endothelial Growth Factor A