Suppression of glomerulosclerosis by adenovirus-mediated IL-10 expression in the kidney
| Autor: | Young Jo Kim, Choi Yk, Jong-Gu Park, Hosun Park, Paik Sg, Lee Yi, Kyu Sam Choi |
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| Rok vydání: | 2003 |
| Předmět: |
Male
medicine.medical_specialty Genetic enhancement Mice Inbred Strains Biology urologic and male genital diseases Kidney Viral vector Adenoviridae Mice Immune system Focal segmental glomerulosclerosis Transduction Genetic Internal medicine Genetics medicine Animals Molecular Biology Proteinuria Glomerulosclerosis Focal Segmental Reverse Transcriptase Polymerase Chain Reaction Glomerulosclerosis Genetic Therapy medicine.disease beta-Galactosidase Interleukin-10 Interleukin 10 medicine.anatomical_structure Endocrinology Molecular Medicine Female medicine.symptom |
| Zdroj: | Gene therapy. 10(7) |
| ISSN: | 0969-7128 |
| Popis: | 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-beta1 (TGF-beta1) 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. |
| Databáze: | OpenAIRE |
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