The Effect of RNA Interference for TGF-beta1 Overexpression in Rat with Unilateral Ureteral Obstruction.
- Author:
Hye Jin KIM
1
;
Hyun Chul KIM
;
Kwan Kyu PARK
Author Information
1. Department of Pathology, Catholic University School of Medicine, Daegu, Korea. kkpark@cu.ac.kr
- Publication Type:Original Article
- Keywords:
RNA interference;
Chronic renal failure;
TGF-beta1;
Fibrosis;
Unilateral ureteral obstruction
- MeSH:
Allografts;
Animals;
Blotting, Western;
Collagen Type I;
Dialysis;
Fibrosis;
Kidney;
Kidney Failure, Chronic;
Mesangial Cells;
Mice;
Polymerase Chain Reaction;
Rats*;
Renal Insufficiency, Chronic;
RNA Interference*;
RNA*;
RNA, Messenger;
RNA, Small Interfering;
Transforming Growth Factor beta1*;
Ureter*;
Ureteral Obstruction*;
Veins
- From:Korean Journal of Nephrology
2005;24(5):739-748
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
BACKGROUND: The progression of chronic renal diseases is an increasingly common condition, often leading to complete destruction of functional kidney tissue and dependency of affected individuals of life- long treatments with dialysis or renal allograft transplantation. The development of irreVersible renal changes in tubulointerstitial fibrosis leads to a loss of kidney function. TGF-beta1 was found to play an important role in the accumulation of extracellualr matrix in kidneys. METHODS: We introduced a RNA interference for TGF-beta1 in mice using the unilateral ureteral obstruction (UUO) model to attenuate interstitial fibrosis by injection of vector into tail vein. The effectiveness of siRNA (small interfering RNA) for TGF-beta1 mRNA sequence was also investigated in the cultured mesangial cells. RESULTS: The levels of TGF-beta1 mRNA was decreased in cultured mesangial cells treated with TGF-beta1 siRNA. TGF-beta1 mRNA was increased markedly in the interstitium of UUO kidneys. RT- PCR and Western blot analysis revealed that the levels of TGF-beta1 and type 1 collagen mRNA were lower in the obstructed kidneys treated with siRNA compared to control uuo kidneys. CONCLUSION: These results demonstrate that the introduction of TGF-beta1 siRNA may be a potential therapeutic maneuver for attenuating interstitial fibrosis.
