- The Effect of Ribbon-Type Antisense Oligodeoxynucleotides for Transforming Growth Factor-beta1 in Unilateral Ureteral Obstruction .
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Sang Mi Han, Eun Joo Kim, Hyo Soon Jeoung, Byung Yuk Lee, Sang Sook Lee, Kwan Kyu Park, Hyun Chul Kim
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Korean J Pathol. 2002;36(2):84-92.
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 Abstract
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- BACKGROUND
In unilateral ureteral obstruction (UUO), the obstructed kidney is characterized by interstitial fibrosis and an increase in transforming growth factor (TGF)-beta1.
Interstitial expression of TGF-beta1 is important in tublointerstitial fibrosis. The objectives of this study is to make new ribbon-type antisense oligodeoxynucleotides (ODN) for TGF-beta1 which are resistant to exonuclease and to examine the effcets of TGF-beta1 on reducing tubulointerstitial fibrosis of the kidney.
METHODS
We introduced a new ribbon-type antisense ODN for TGF-beta1 in rats using the UUO model to block interstitial fibrosis by tail vein injection. A combination of one antisense sequences for TGF-beta1 was adopted to construct a large antisense molecule with a loop and stem. Artificial viral envelope (AVE)-type hemagglutinating virus of Japan (HVJ)-liposomes were used as a vector system for the delivery of antisense ODN.
RESULTS
The levels of TGF-beta1 mRNA was decreased more in the cultured mesangial cells treated with ribbon-type antisense ODN than in that of a linear-type antisense ODN for TGF-beta1. TGF-beta1 mRNA was increased markedly in the interstitium of untreated obstructed kidneys. Northem analysis revealed that the levels of TGF-beta1 mRNA were decreased in the obstructed kidneys treated with antisense ODN. The fibrosis of the obstructed kidneys treated with ribbon-type antisense ODN was dramatically less than that of the untreated group.
CONCLUSIONS
These results demonstrate that the introduction of new ribbon-type antisense ODN for TGF-beta1 may be a potential therapeutic maneuver for preventing interstitial fibrosis.
- The Effect of Antibody and Gene Therapy for Transforming Growth Factor- 1 on Scar Formation.
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Jun Hyung Kim, Ki Hwan Han, Jong Duck Ahn, In Kyu Lee, Eun Joo Kim, Mee Yul Hwang, Kwan Kyu Park
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Korean J Pathol. 2001;35(5):424-432.
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Abstract
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- BACKGROUND
Transforming growth factor (TGF)- has a large variety of biological functions, including the modulation of inflammation and the immune system, and is presumed to play important roles in repairing wounds and reducing scarring.
The objective of this study is to examine the effects of TGF-1 on healing wounds and reducing scarring. We have also analysed the ability of the hemagglutinating virus of Japan (HVJ) liposome mediated antisense oligodeoxynucleotides (ODNs) to specifically inhibit wound-induced expressions of TGF-1 proteins and mRNA in the rat skin.
METHODS
Skin wounds were created on the backs of 80 anesthetized rats. The first group of wounds, as the controls, was unmanipulated. The second group of wounds, as positive controls or an excessive scarring model, was injected with TGF-1 subcutaneously. The third group of wounds was injected with anti-TGF-1 antibody subcutaneously.
The fourth group of wounds was injected with HVJ liposome mediated antisense ODNs for TGF-1 subcutaneously. The wounds of all groups were bisected and analysed histologically 5, 10, 15, 30, and 50 days after the wounds were made.
RESULTS
All control wounds (TGF-1 or no injection) healed with scarring, whereas the wounds treated with the antibody or antisense ODNs healed with less scar formation compared to the control group. The wounds treated with the antibody or antisense ODNs had fewer macrophages, less collagen and fibronectin contents than the other wounds. Northern blotting and in situ hybridization analysis showed that wound sites treated with HVJ liposome mediated antisense ODNs for TGF-1 exhibited decreased levels of TGF-1 mRNA after injury.
CONCLUSIONS
These findings suggest an important new approach to controlling scarring in normal wound healing, complementing the practice of adding exogenous growth factors to chronic wounds in the attempt to inhibit collagen deposition.
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