TGF-β1 siRNA suppresses the tubulointerstitial fibrosis in the kidney of ureteral obstruction

TGF-beta 1 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-1 function in unilateral ureteral obstruction (UUO)-induced renal fibrosis. shRNA vectors were generated to suppress TGF-beta 1 expression at a high glucose concentration which allowed the maximal induction of TGF-1 in primary rat mesangial cells. An shRNA vector, designated shTB1d, significantly suppressed TGF-beta 1 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 1 collagen and PAI-1) of TGF-beta 1. Furthermore, the shTB1d suppressed the expression of TGF-beta 1 and type 1 collagen in tabulointerstitial cells until day 7 after UUO-induced fibrosis, but none- or vector-treated mice maintained their expression, suggesting that the TGF-beta 1 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. (c) 2005 Elsevier Inc. All rights reserved.