Document Detail


Rapamycin attenuates unilateral ureteral obstruction-induced renal fibrosis.
MedLine Citation:
PMID:  16732193     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Unilateral ureteral obstruction (UUO) is a well-characterized hydronephrosis model exhibiting interstitial inflammatory-cell infiltration and tubular dilatation followed by tubulointerstitial fibrosis of the obstructed kidney. Our recent report indicates that rapamycin is effective for 50% of transplant recipients with chronic allograft nephropathy. In this study, we investigate the effect of rapamycin on UUO-induced renal fibrosis. UUO or sham-operated rats were randomly assigned to rapamycin or vehicle and were killed on days 7 and 14 after UUO or sham operation. Rapamycin decreased cross-sectional and gross-morphology changes in the obstructed kidney significantly. Rapamycin markedly blunted the increase in weight of the obstructed kidney, obstructed kidney length, and the obstructed/non-obstructed kidney weight ratio (by 74.6, 42.8, and 61.6% on day 14, respectively, all P<0.01). The scores for tubular dilatation, interstitial volume, interstitial collagen deposition, and alpha-smooth muscle actin (alpha-SMA) after UUO were significantly reduced by rapamycin. Rapamycin also decreased the number of infiltrative anti-ED1-positive cells and the gene expression of transforming growth factor (TGF)-beta1 (84.8 and 80.2% on day 7) after UUO (both P<0.01). By double immunostaining and Western analysis, rapamycin blocked the TGF-beta1-induced loss of E-cadherin expression and de novo increase of the expression of alpha-SMA in a dose-dependent manner. In conclusion, rapamycin significantly attenuated tubulointerstitial damage in a UUO-induced rat model of renal fibrosis, suggesting that rapamycin may have the potential to delay the progression of tubulointerstitial renal fibrosis.
Authors:
M-J Wu; M-C Wen; Y-T Chiu; Y-Y Chiou; K-H Shu; M-J Tang
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Kidney international     Volume:  69     ISSN:  0085-2538     ISO Abbreviation:  Kidney Int.     Publication Date:  2006 Jun 
Date Detail:
Created Date:  2006-05-29     Completed Date:  2006-10-26     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0323470     Medline TA:  Kidney Int     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2029-36     Citation Subset:  IM    
Affiliation:
Division of Nephrology, Department of Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.
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MeSH Terms
Descriptor/Qualifier:
Animals
Fibrosis / etiology,  prevention & control
Immunosuppressive Agents / therapeutic use*
Kidney / pathology*
Male
Rats
Rats, Sprague-Dawley
Sirolimus / therapeutic use*
Ureteral Obstruction / complications*
Chemical
Reg. No./Substance:
0/Immunosuppressive Agents; 53123-88-9/Sirolimus
Comments/Corrections
Comment In:
Kidney Int. 2006 Jun;69(11):1925-7   [PMID:  16724087 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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