Prevention of tissue injury by ribbon antisense to TGF-β1 in the kidney
Transforming growth factor-beta1 (TGF-β1) is an important mediator of glomerulosclerosis and tubulointerstitial fibrosis in renal diseases. We designed ribbon-type antisense oligos of TGF-β1, TGF-β1 RiAS, and combined them with a short peptide of the nuclear localization signal to form a transfection complex of DNA/peptide/liposomes (DPL) for enhanced cellular uptake. When H4IIE cells were transfected with TGF-β1 RiAS, the level of TGF-β1 mRNA was reduced by >70%. We then examined the ratio of the kidney weight per body weight in rats. Whereas the weight ratio was 0.47% for the normal kidney, the ratio was 0.99% on day 5 after unilateral ureteric obstruction (UUO). The ratios were 0.95% with PBS injection, 1.07% with scrambled RiAS, and 0.68% with TGF-β1 RiAS. When examined for TGF-β1 expression in the tissue, the level of TGF-β1 mRNA was also significantly reduced following treatment with TGF-β1 RiAS. Further, physical changes such as diminished dilation, atrophy, as well as apoptosis caused by UUO were also found to be markedly reduced by TGF-β1 RiAS. The results show that ribbon antisense to TGF-β1 when combined with efficient uptake can effectively block TGF-β1 expression and preserve tissue integrity in kidneys with UUO.
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Document Type: Research Article
Affiliations: Department of Medical Genetic Engineering, Keimyung University School of Medicine, Daegu, Korea
Publication date: March 1, 2005
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- The International Journal of Molecular Medicine is a monthly, peer-reviewed journal devoted to the publication of high quality studies related to the molecular mechanisms of human disease. The journal welcomes research on all aspects of molecular and clinical research, ranging from biochemistry to immunology, pathology, genetics, human genomics, microbiology, molecular pathogenesis, molecular cardiology, molecular surgery and molecular psychology.
The International Journal of Molecular Medicine aims to provide an insight for researchers within the community in regard to developing molecular tools and identifying molecular targets for the diagnosis and treatment of a diverse number of human diseases.
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