Korean J Nephrol.  2005 Sep;24(5):739-748.

The Effect of RNA Interference for TGF-beta1 Overexpression in Rat with Unilateral Ureteral Obstruction

• Kim HJ
• Kim HC
• Park KK

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.

Keyword

RNA interference; Chronic renal failure; TGF-beta1; Fibrosis; Unilateral ureteral obstruction

MeSH Terms

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
Collagen Type I
RNA
RNA, Messenger
RNA, Small Interfering
Transforming Growth Factor beta1