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KMID : 0357920020360020084
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Korean Journal of Pathology
2002 Volume.36 No. 2 p.84 ~ p.92
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The Effect of Ribbon-Type Antisense Oligodeoxynucleotides for Transforming Growth Facotor-β1 in Unilateral Ureteral obstruction
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Han Sang-Mi
Kim Hyun-Chul
Park Kwan-Kyu
Lee Sang-Sook
Kim Eun-Joo
Jeoung Hyo-Soon
Lee Byung-Yuk
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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)-β1. Interstitial expression of TGF-β1 is important in tublointersitial fibrosis. The objectives of this study is to male new ribbon-type antisense oligodeoxynucletides (ODN) for TGF-β1 which are resistant to exonuclease and to examine the effects of TGF-β1 on reducing tubulointerstitial fibrosis of the kidney.
Methods: We introduced a new ribbon-type antisense ODN for TGF-β1 in rats using the UUO model to block interstitial fibrosis by tail vein injection. A combination of one antisense sequences for TGF-β1 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-β1 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-β1. TGF-β1 mRNA was increased markedly in the intersitium of untreated obstructed kidneys. Northem analysis revealed that the levels of TGF-β1 mRNA were decreased in the obstructed kidneys 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-β1 may be a potential therapecutic maneuver for preventing interstitial fibrosis.
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KEYWORD
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Models, Animal, Gene Therapy, Transforming Growth Factor-beta, Ureteral Obstruction
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