TGF-beta1 siRNA suppresses the tubulointerstitial fibrosis in the kidney of ureteral obstruction.
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.
Hwang
Meeyul
M
Department of Pathology, Catholic University of Daegu School of Medicine, Daegu, Republic of Korea.
Kim
Hye-Jin
HJ
Noh
Hey-Jeong
HJ
Chang
Young-Chae
YC
Chae
Young-Mi
YM
Kim
Kyung-Hyun
KH
Jeon
Jae-Pil
JP
Lee
Tae-Sung
TS
Oh
Hoon-Kyu
HK
Lee
Yun-Sik
YS
Park
Kwan-Kyu
KK
D000818:Animals; D005355:Fibrosis; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000235:genetics; D005920:Glomerular Mesangium / Q000473:pathology; D005947:Glucose; D066298:In Vitro Techniques; D007674:Kidney Diseases / Q000209:etiology / Q000473:pathology* / Q000517:prevention & control*; D007684:Kidney Tubules / Q000473:pathology*; D051379:Mice; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics*; D051381:Rats; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D053773:Transforming Growth Factor beta1; D014517:Ureteral Obstruction / Q000150:complications / Q000473:pathology*
D034741:RNA, Small Interfering; C508961:Tgfb1 protein, mouse; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D005947:Glucose