Upregulated Expression of Transforming Growth Factor-.BETA., Type IV Collagen, and Plasminogen Activator Inhibitor-1 mRNA Are Decreased after Release of Unilateral Ureteral Obstruction.

Abstract

Tubulointerstitial fibrosis is a major cause of irreversible renal damage in the obstructed kidney. The effects of release of obstruction on the obstructed kidney are not clearly understood. We investigated the effects of the release of ureteral obstruction on renal fibrosis and the expression of fibrogenic factors. Rats underwent 5 day of unilateral ureteral obstruction (UUO). After release of obstruction by removing an encased rubber tube, changes in interstitial volume were morphologically evaluated and the mRNA expression of transforming growth factor-beta (TGF-beta), type IV collagen (collagen IV), and plasminogen activator inhibitor-1 (PAI-1) were examined by reverse transcription-polymerase chain reaction (RT-PCR) up to 28 days. Renal interstitial volume, collagen IV and PAI-1 mRNA gradually decreased from 7 days to 28 days after release of obstruction. However, increased expression of TGF-beta mRNA persisted up to 14 days, and then declined 28 days after release. In conclusion, obstruction-induced renal fibrosis was recovered with diminished expression of TGF-beta and collagen IV. Decreased PAI-1 expression in the post-obstructed kidney may contribute to the degradation of extracellular matrix proteins and recovery of tubulointerstitial fibrosis, at least partly, after release of ureteral obstruction.