Rapamycin attenuates unilateral ureteral obstruction-induced renal fibrosis

doi:10.1038/sj.ki.5000161

中山醫學大學機構典藏 CSMUIR > 醫學院 > 醫學系 > 期刊論文 > Item 310902500/4357

Please use this identifier to cite or link to this item: https://ir.csmu.edu.tw:8080/ir/handle/310902500/4357

Title:	Rapamycin attenuates unilateral ureteral obstruction-induced renal fibrosis
Authors:	Wu, M-J Wen, M-C Chiu, Y-T Chiou, Y-Y Shu, K-H Tang, M-J
Contributors:	中山醫學大學醫學系
Keywords:	rapamycin renal fibrosis unilateral ureteral obstruction (UUO)
Date:	2005-10-05
Issue Date:	2012-07-23T08:01:04Z (UTC)
ISSN:	0085-2538
Abstract:	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 -smooth muscle actin (-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)-1 (84.8 and 80.2% on day 7) after UUO (both P<0.01). By double immunostaining and Western analysis, rapamycin blocked the TGF-1-induced loss of E-cadherin expression and de novo increase of the expression of -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.
URI:	https://ir.csmu.edu.tw:8080/ir/handle/310902500/4357 http://dx.doi.org/10.1038/sj.ki.5000161
Relation:	Original Articles Kidney International (2006) 69, 2029–2036
Appears in Collections:	[醫學系] 期刊論文

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