TGF-beta1 siRNA suppresses the tubulointerstitial fibrosis in the kidney of ureteral obstruction.

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.

• Authors: Meeyul Hwang, Hye-Jin Kim, Hey-Jeong Noh, Young-Chae Chang, Young-Mi Chae, Kyung-Hyun Kim, Jae-Pil Jeon, Tae-Sung Lee, Hoon-Kyu Oh, Yun-Sik Lee, Kwan-Kyu Park
• Journal: Experimental and molecular pathology (Exp Mol Pathol) Vol. 81 Issue 1 Pg. 48-54 (Aug 2006) ISSN: 0014-4800 [Print] Netherlands
• PMID: 16443218 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• RNA, Small Interfering
• Tgfb1 protein, mouse
• Tgfb1 protein, rat
• Transforming Growth Factor beta
• Transforming Growth Factor beta1
• Glucose

Topics

• Animals
• Fibrosis
• Genetic Therapy
• Genetic Vectors (genetics)
• Glomerular Mesangium (pathology)
• Glucose
• In Vitro Techniques
• Kidney Diseases (etiology, pathology, prevention & control)
• Kidney Tubules (pathology)
• Mice
• RNA Interference
• RNA, Small Interfering (genetics)
• Rats
• Transforming Growth Factor beta (antagonists & inhibitors, genetics, metabolism)
• Transforming Growth Factor beta1
• Ureteral Obstruction (complications, pathology)