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Losartan Alleviates Renal Fibrosis by Down-Regulating HIF-1αand Up-Regulating MMP-9/TIMP-1 in Rats with 5/6 Nephrectomy
| Content Provider | Scilit |
|---|---|
| Author | Fu, Wencheng Wang, Yunman Jin, Zhouhui Wang, Hao Cheng, Weiwei Zhou, Haishan Yin, Peihao Peng, Wen |
| Copyright Year | 2012 |
| Description | Journal: Renal Failure Background: This study investigated the effects of losartan intervention on the expressions of hypoxia-inducible factor-1α (HIF-1α), matrix metalloproteinase-9 (MMP-9), and tissue inhibitor of metalloproteinase-1 (TIMP-1) in renal fibrosis in rats with 5/6 nephrectomy. Methods: Sprague Dawley rats were randomly divided into three groups. Rats in the losartan group were gavaged with losartan (33.3 mg/kg/day) from 1 week after 5/6 nephrectomy, and those in the sham group and the model group only received an equal volume of saline solution by gavage. Rats were sacrificed at the ends of the 4, 8 and 12 weeks, respectively. Urinary N-acetyl-glucosaminidase (NAG), 24-h urinary protein, serum cystatin C, blood urea nitrogen (BUN), and serum creatinine (Scr) levels were assessed. Kidney tissues were observed under light and electron microscope. The expressions of HIF-1α, transforming growth factor-β1 (TGF-β1), MMP-9, and TIMP-1 were determined by immunohistochemistry and Western blotting. Results: Twenty-four hour urinary protein, urinary NAG, serum cystatin C, BUN, and Scr levels in the model group were significantly higher than those in the sham group (p < 0.05), but losartan treatment improved these changes. The apparent glomerular sclerosis and tubulointerstitial fibrosis were also found in the model group, which were ameliorated by losartan. The expressions of HIF-1α, TGF-β1, MMP-9, and TIMP-1 were elevated and MMp-9/TIMP-1 ratio was lowered in the model group (p < 0.05), but losartan increased the expression of MMP-9 and MMp-9/TIMP-1 ratio (p < 0.05) and lessened the expressions of HIF-1α, TGF-β1, and TIMP-1 (p < 0.05). Conclusion: Losartan may ameliorate renal fibrosis partly by down-regulating HIF-1α and up-regulating MMP-9/TIMP-1 in rats with 5/6 nephrectomy. |
| Related Links | https://www.tandfonline.com/doi/pdf/10.3109/0886022X.2012.723775?needAccess=true |
| Ending Page | 1304 |
| Page Count | 8 |
| Starting Page | 1297 |
| ISSN | 0886022X |
| e-ISSN | 15256049 |
| DOI | 10.3109/0886022x.2012.723775 |
| Journal | Renal Failure |
| Issue Number | 10 |
| Volume Number | 34 |
| Language | English |
| Publisher | Informa UK Limited |
| Publisher Date | 2012-08-08 |
| Access Restriction | Open |
| Subject Keyword | Journal: Renal Failure Integrative and Complementary Medicine Renal Fibrosis Hypoxia Inducible Factor-1α Matrix Metalloproteinase-9 Tissue Inhibitor of Metalloproteinase-1 |
| Content Type | Text |
| Subject | Critical Care and Intensive Care Medicine Nephrology |
