Korean Journal of Nephrology 2008;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
Ji-Young Choi, M.D., Mi-Kyung Jin, M.D., Joo-Hyun Chun, M.D., Seung-Hyea Hyun, M.D., Hee-Jeong Choi, M.D., Hyuk-Joon Choi, M.D., Ji-Hyung Cho, M.D., Mi-Hyung Kim, Hye-Myung Ryu, Eun-Joo Oh, Soon-Youn Choi, Chan-Duck Kim, M.D., Yong-Lim Kim, M.D. and Sun-H
Department of Internal Medicine, Kyungpook National University, School of Medicine, Daegu, Korea
기초연구 : 복막투석 동물모델에서 Adenoviral vector를 이용한 Bone Morphogenic Protein-7 유전자 치료가 복막섬유화에 미치는 영향
최지영, 진미경, 전주현, 현승혜, 최희정, 최혁준, 조지형, 김미형, 류혜명, 오은주, 최순연, 김찬덕, 김용림, 박선희
경북대학교 의학전문대학원 내과학교실
Abstract
Purpose : TGF-β-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-β, VEGF, laminin and aquaporin-1 was performed in addition to morphometric analysis of peritoneum. Immunofluorescence staining with western blotting for α-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-β1 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.
Key Words: Gene therapy, Bone morphogenetic protein 7, Transforming growth factor-β, Peritoneal dialysis


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