Prevention of tissue injury by ribbon antisense to TGF-β1 in the kidney
- Affiliated Author(s)
- 장병철; 박종구; 서성일
- Alternative Author(s)
- Jang, Byeong Churl; Park, Jong Gu; Suh, Seong Il
- Journal Title
- International Journal of Molecular Medicine
- ISSN
- 1107-3756
- Issued Date
- 2005
- Abstract
- 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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