The Effect of Ribbon-Type Antisense Oligodeoxynucleotides for Transforming Growth Factor-beta1 in Unilateral Ureteral Obstruction
Korean Journal of Pathology
;
: 84-92, 2002.
Article
in Korean
| WPRIM
| ID: wpr-51629
ABSTRACT
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.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Oligodeoxyribonucleotides
/
Ureter
/
Ureteral Obstruction
/
Veins
/
Fibrosis
/
RNA, Messenger
/
Transforming Growth Factors
/
Sendai virus
/
Mesangial Cells
/
Transforming Growth Factor beta1
Type of study:
Prognostic study
Limits:
Animals
Language:
Korean
Journal:
Korean Journal of Pathology
Year:
2002
Type:
Article
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