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  • Title: TGF-beta1 siRNA suppresses the tubulointerstitial fibrosis in the kidney of ureteral obstruction.
    Author: Hwang M, Kim HJ, Noh HJ, Chang YC, Chae YM, Kim KH, Jeon JP, Lee TS, Oh HK, Lee YS, Park KK.
    Journal: Exp Mol Pathol; 2006 Aug; 81(1):48-54. PubMed ID: 16443218.
    Abstract:
    TGF-beta1 has been known as an important factor in tubulointerstitial fibrosis which is a common process in most progressive renal diseases. We hypothesized that the interstitial fibrosis could be prevented by abolishing TGF-beta1 function in unilateral ureteral obstruction (UUO)-induced renal fibrosis. shRNA vectors were generated to suppress TGF-beta1 expression at a high glucose concentration which allowed the maximal induction of TGF-beta1 in primary rat mesangial cells. An shRNA vector, designated shTB1d, significantly suppressed TGF-beta1 in both transcriptional and translational levels in vitro cultured cells and in vivo fibrosis-induced mouse kidney, accompanied by the suppression of target genes (e.g., type I collagen and PAI-1) of TGF-beta1. Furthermore, the shTB1d suppressed the expression of TGF-beta1 and type I collagen in tubulointerstitial cells until day 7 after UUO-induced fibrosis, but none- or vector-treated mice maintained their expression, suggesting that the TGF-beta1 shRNA delays the process of renal fibrosis in UUO mouse model. This work would provide a valuable tool to prevent tubulointerstitial fibrosis using RNA interference strategy.
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