편측성 요관 폐쇄모델에서 Transtforming Growth Factor-β1 mRNA에 대한 리본형 Antisense Oligodeoxynucleotide 의 유전자 치료 효과
The Effect of Ribbon-Type Antisense Oligodeoxynucleotides for Transforming Growth Facotor-β1 in Unilateral Ureteral obstruction
한상미, 김현철, 박관규, 이상숙, 김은주, 정효순, 이병육,
소속 상세정보
한상미 ( Han Sang-Mi )
계명대학교 의과대학 병리학교실
김현철 ( Kim Hyun-Chul )
계명대학교 신장연구소
박관규 ( Park Kwan-Kyu )
계명대학교 의과대학 병리학교실
이상숙 ( Lee Sang-Sook )
계명대학교 의과대학 병리학교실
김은주 ( Kim Eun-Joo )
계명대학교 의과대학 병리학교실
정효순 ( Jeoung Hyo-Soon )
계명대학교 의과대학 병리학교실
이병육 ( Lee Byung-Yuk )
계명대학교 의과대학 병리학교실
KMID : 0357920020360020084
Abstract
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.
키워드
Models;Animal;Gene Therapy;Transforming Growth Factor-beta;Ureteral Obstruction
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