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Suppression of glomerulosclerosis by adenovirus-mediated IL-10 expression in the kidney

Gene Therapy volume 10, pages 559–568 (2003)Cite this article

Abstract

Glomerulosclerosis is a common morphologic result seen in almost all progressed renal diseases, and is the characteristic change in focal segmental glomerulosclerosis (FSGS). The most convincing hypothesis for glomerulosclerosis is cytokine-mediated injury by infiltrating immune cells in the glomerulus and tubulointerstitial area. This study investigated whether the anti-inflammatory effect of interleukin-10 (IL-10) when expressed by a recombinant adenoviral vector can prevent the onset of glomerulosclerosis in FGS/Kist mice (an animal model with naturally occurring renal failure initiated by FSGS). Each group of mice received recombinant adenoviruses encoding human IL-10 (Ad:hIL-10) by intraparenchymal injection at 6 weeks and were examined for cytokine expression, glomerular sclerotic index, and proteinuria. After injection of Ad:hIL-10 to the kidney, IL-10 expression was found to last over 20 days. Mice treated with Ad:hIL-10 were shown to have a significant reduction in the glomerular sclerotic index at 10 weeks when compared to control groups. The level of proteinuria in Ad:hIL-10-treated mice was also significantly reduced. About 50% of the urine samples of naive and Ad:LacZ-treated groups had severe levels of proteinuria. By contrast, at 10 weeks the group treated with Ad:hIL-10 had lower levels of proteinuria and transforming growth factor-β1 (TGF-β1) expression. These results demonstrate that IL-10 effectively prevents the development of glomerulosclerosis in FGS/Kist mice, and IL-10 gene therapy may be of use for the treatment of renal failure.

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Acknowledgements

The authors thank Drs Beughwa Hyun and Chulholee at Korea Research Institute of Bioscience and Biotechnology, for providing FGS/kist mice for this work. This work was supported by research grants from the SRC of Sunkyunkwan University (MTRC), the Korea Science & Engineering Foundation (R01-2000-00138) and WelGENE Pharmaceuticals Inc., a biotechnology company founded by Dr Park.

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Authors and Affiliations

  1. Department of Medical Genetic Engineering, Keimyung University School of Medicine, Daegu, Republic of Korea

    Y-K Choi, K Choi & J-G Park

  2. Department of Pathology, Yeungnam University College of Medicine, Daegu, Republic of Korea

    Y-J Kim

  3. Department of Microbiology, Yeungnam University College of Medicine, Daegu, Republic of Korea

    H-S Park

  4. Department of Biology, Chungnam University College of Natural Sciences, Daejeon, Republic of Korea

    S-G Paik

  5. Liver Cell Signal Transduction Research, Korea Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea

    Y-I Lee

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Choi, YK., Kim, YJ., Park, HS. et al. Suppression of glomerulosclerosis by adenovirus-mediated IL-10 expression in the kidney. Gene Ther 10, 559–568 (2003). https://doi.org/10.1038/sj.gt.3301926

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