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KMID : 0359920080270040421
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Korean Journal of Nephrology
2008 Volume.27 No. 4 p.421 ~ p.432
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The Effect of Adenoviral-mediated Gene Transfer of Bone Morphogenic Protein-7 on Peritoneal Fibrosis in an Animal Model of Peritoneal Dialysis
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Choi Ji-Young
Choi Hee-Joung
Jin Mi-Kyung
Chun Joo-Hyun
Hyun Seung-Hyea
Cho Ji-Hyung
Park Sun-Hee
Kim Yong-Lim
Kim Chan-Duck
Ryu Hye-Myung
Choi Hyuk-Joon
Kim Mi-Hyung
Oh Eun-Joo
Choi Soon-Youn
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Abstract
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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.
Conclusion: 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.
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KEYWORD
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Gene therapy, bone morphogenetic protein 7, Transforming growth t\factor-β, peritoneal dialysis
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