Journal
CELLULAR PHYSIOLOGY AND BIOCHEMISTRY
Volume 33, Issue 5, Pages 1316-1328Publisher
KARGER
DOI: 10.1159/000358699
Keywords
Astragaloside IV; Wnt/beta-catenin signaling pathway; UUO model; Renal interstitial fibrosis
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Funding
- General Medicine of Key Discipline Construction Project
- State Administration of Traditional Chinese Medicine of the People's Republic of China
- Leading Academic Discipline Project of State Administration of Traditional Chinese Medicine of China
- Talent Project of Integrative Medicine of Shanghai Municipal Health Bureau [ZYSNXD012-RC-ZXY]
- Key Medical Discipline Project of Shanghai Municipal Health Bureau [ZK2012A34]
- Independent Innovation Research Fund of Putuo District Science and Technology Committee [2012PTKW002]
- Budget Project of Shanghai Municipal Education Commission [2012JW71]
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Objective: To investigate the effect of Astragaloside IV (AS-IV) on the regulation of the Wnt/beta-catenin signaling pathway in rats with unilateral ureteral obstruction (UUO). Methods: Rat renal interstitial fibrosis models were prepared using unilateral ureteral ligation. Rats were randomly divided into sham group, sham group with AS-IV (33mg/kg), unilateral ureteral obstruction group, and unilateral ureteral obstruction group receiving varied doses of AS-IV (3.3, 10, and 33 mg/kg). Immunohistochemical analysis, real-time fluorescence quantitative PCR (FQ-PCR), and western blot were used to detect the expression of genes and proteins associated with the Wnt/beta-catenin signaling pathway in renal tissues. Results: Levels of Wnt3, Wnt4, and Frizzled gene expression increased significantly in the UUO model; AS-IV was associated with the downregulation of the expression of Wnt3, Wnt4, Frizzled4, p-LRP5, p-LRP6, disheveled, beta-catenin, LEF-1, TCF-1, Snail, Jagged 1, Twist, MMP2, and MMP7 proteins in a concentration-dependent manner, while the expression of APC, CK1, and E-cadherin was increased. Conclusions: AS-IV effectively inhibits the up-regulation of proteins in the Wnt/beta-catenin signaling pathway in UUO-model rats, indicating its possible inhibitory effects on renal interstitial fibrosis. Copyright (C) 2014 S. Karger AG, Basel
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