Losartan attenuates renal interstitial fibrosis and tubular cell apoptosis in a rat model of obstructive nephropathy

He,Ping; Li,Detian; Zhang,Beiru

doi:10.3892/mmr.2014.2304

Losartan attenuates renal interstitial fibrosis and tubular cell apoptosis in a rat model of obstructive nephropathy

Authors:
- Ping He
- Detian Li
- Beiru Zhang
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Affiliations: Department of Nephrology, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China
Published online on: June 6, 2014 https://doi.org/10.3892/mmr.2014.2304
Pages: 638-644

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Abstract

Ureteral obstruction leads to renal injury and progresses to irreversible renal fibrosis, with tubular cell atrophy and apoptosis. There is conflicting evidence concerning whether losartan (an angiotensin II type I receptor antagonist) mitigates renal interstitial fibrosis and renal tubular epithelial cell apoptosis following unilateral ureteral obstruction (UUO) in animal models. The aim of this study was to investigate the effect and mechanism of losartan on renal tubular cell apoptosis and renal fibrosis in a rat model of UUO. The rats were subjected to UUO by ureteral ligation and were treated with dimethyl sulfoxide (control) or losartan. The controls underwent sham surgery. The renal tissues were collected 3, 5, 7 and 14 days after surgery for measurement of various indicators of renal fibrosis. UUO increased the expression levels of α‑smooth muscle actin and collagen I, and the extent of renal tubular fibrosis and apoptosis in a time‑dependent manner. Losartan treatment partially attenuated these responses. Progression of renal interstitial fibrosis was accompanied by phosphorylation of signal transducer and activator of transcription 3 (STAT3) and altered the expression levels of two apoptosis‑related proteins (Bax and Bcl2). Losartan treatment also partially attenuated these responses. The results indicated that losartan attenuated renal fibrosis and renal tubular cell apoptosis in a rat model of UUO. This effect appeared to be mediated by partial blockage of STAT3 phosphorylation.

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