OBJECTIVE: To investigate the effect of Astragaloside IV (AS-IV) on the regulation of the Wnt/β-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/β-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, β-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/β-catenin signaling pathway in UUO-model rats, indicating its possible inhibitory effects on renal interstitial fibrosis.
OBJECTIVE: To investigate the effect of Astragaloside IV (AS-IV) on the regulation of the Wnt/β-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/β-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, β-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/β-catenin signaling pathway in UUO-model rats, indicating its possible inhibitory effects on renal interstitial fibrosis.
Authors: Catherina A Cuevas; Cheril Tapia-Rojas; Carlos Cespedes; Nibaldo C Inestrosa; Carlos P Vio Journal: Biomed Res Int Date: 2015-04-07 Impact factor: 3.411