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편측성 요관 폐쇄모델에서 Transforming Growth Factor-β1 mRNA에 대한 리본형 Antisense Oligodeoxynucleotide의 유전자 치료 효과

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Author(s)
한상미김은주정효순이병육이상숙박관규김현철
Keimyung Author(s)
Lee, Sang SookPark, Kwan KyuKim, Hyun Chul
Department
Dept. of Pathology (병리학)
Dept. of Internal Medicine (내과학)
Kidney Institute (신장연구소)
Journal Title
대한병리학회지
Issued Date
2002
Volume
36
Issue
2
Abstract
Background : In unilateral ureteral obstruction (UUO), the obstructed kidney is characterized by interstitial fibrosis and an increase in transforming growth factor (TGF)- 1. Interstitial expression of TGF- 1 is important in tublointerstitial fibrosis. The objectives of this study is to make new ribbon-type antisense oligodeoxynucleotides (ODN) for TGF- 1 which are resistant to exonuclease and to examine the effects of TGF- 1 on reducing tubulointerstitial fibrosis of the kidney.
Methods : We introduced a new ribbon-type antisense ODN for TGF- 1 in rats using the UUO model to block interstitial fibrosis by tail vein injection. A combination of one antisense sequences for TGF- 1 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- 1 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- 1. TGF- 1 mRNA was increased markedly in the interstitium of untreated obstructed kidneys. Northern analysis revealed that the levels of TGF- 1 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- 1 may be a potential therapeutic maneuver for preventing interstitial fibrosis.
Key Words : Models, Animal-Gene Therapy-Transforming Growth Factor-beta-Ureteral Obstruction
Alternative Title
The Effect of Ribbon-Type Antisense Oligodeoxynucleotides for Transforming Growth Factor-β1 in Unilateral Ureteral Obstruction
Keimyung Author(s)(Kor)
이상숙
박관규
김현철
Publisher
School of Medicine
Citation
한상미 et al. (2002). 편측성 요관 폐쇄모델에서 Transforming Growth Factor-β1 mRNA에 대한 리본형 Antisense Oligodeoxynucleotide의 유전자 치료 효과. 대한병리학회지, 36(2), 84–92.
Type
Article
ISSN
0379-1149
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/38637
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Internal Medicine (내과학)
1. School of Medicine (의과대학) > Dept. of Pathology (병리학)
3. Research Institutues (연구소) > Kidney Institute (신장연구소)
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