| Rapamycin attenuates unilateral ureteral obstruction-induced renal fibrosis. | |
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MedLine Citation:
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PMID: 16732193 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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M-J Wu; M-C Wen; Y-T Chiu; Y-Y Chiou; K-H Shu; M-J Tang |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Kidney international Volume: 69 ISSN: 0085-2538 ISO Abbreviation: Kidney Int. Publication Date: 2006 Jun |
Date Detail:
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Created Date: 2006-05-29 Completed Date: 2006-10-26 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0323470 Medline TA: Kidney Int Country: United States |
Other Details:
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Languages: eng Pagination: 2029-36 Citation Subset: IM |
Affiliation:
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Division of Nephrology, Department of Medicine, Taichung Veterans General Hospital, Taichung, Taiwan. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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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:
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0/Immunosuppressive Agents; 53123-88-9/Sirolimus |
| Comments/Corrections | |
Comment In:
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Kidney Int. 2006 Jun;69(11):1925-7
[PMID:
16724087
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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