The Effect of Adenoviral-mediated Gene Transfer of Bone Morphogenic Protein-7 on Peritoneal Fibrosis in an Animal Model of Peritoneal Dialysis.
- Author:
Ji Young CHOI
1
;
Mi Kyung JIN
;
Joo Hyun CHUN
;
Seung Hyea HYUN
;
Hee Jeong CHOI
;
Hyuk Joon CHOI
;
Ji Hyung CHO
;
Mi Hyung KIM
;
Hye Myung RYU
;
Eun Joo OH
;
Soon Youn CHOI
;
Chan Duck KIM
;
Yong Lim KIM
;
Sun Hee PARK
Author Information
1. Department of Internal Medicine, Kyungpook National University, School of Medicine, Daegu, Korea. sh-park@knu.ac.kr
- Publication Type:Original Article
- Keywords:
Gene therapy;
Bone morphogenetic protein 7;
Transforming growth factor-beta;
Peritoneal dialysis
- MeSH:
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
- From:Korean Journal of Nephrology
2008;27(4):421-432
- CountryRepublic of Korea
- Language:Korean
-
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.
