Tripterygium�wilfordii mitigates hyperglycemia-induced upregulated Wnt/β-catenin expression and kidney injury in diabetic rats

Abstract

Aberrant activation of the Wnt/β-catenin pathway contributes to the development of diabetic nephropathy (DN); however, treatment with Tripterygium wilfordii (TW) may be beneficial for patients with DN. The aim of the present study was to evaluate the effect of TW on Wnt/β-catenin expression in the kidneys of diabetic rats. Male Sprague-Dawley rats were randomly injected with vehicle (control) or streptozotocin to induce diabetes. Diabetic rats were then randomly treated with vehicle (sodium carboxymethyl cellulose; SCC), TW combined with SCC (8 or 16 mg/kg) or irbesartan (50 mg/kg) daily for 8 weeks. Metabolic parameter levels and renal pathological changes were examined. mRNA and protein expression of Wnt-1, glycogen synthase kinase (GSK)-3β, β-catenin, nuclear factor (NF)-κB and transforming growth factor (TGF)-β1 in the kidneys of rats from all groups were measured. Compared with the DM group, metabolic parameters and morphological parameters, apart from blood glucose levels, were significantly improved in TW-treated rats (all P<0.01). Furthermore, levels of Wnt-1, β-catenin, NF-κB-p65 and TGF-β1 mRNA and protein were significantly reduced in the kidneys of TW-treated rats compared with DM rats, whereas levels of GSK-3β mRNA and protein did not differ significantly between any of the groups; however, the expression of P-GSK-3β protein was significantly decreased in the kidneys of TW-treated rats compared with the DM group. The protective effects of TW tended to be dose-dependent and were an improvement compared with irbesartan treatment in diabetic rats. Therefore, the results of the present study indicated that treatment with TW mitigated hyperglycemia-induced upregulated Wnt-1 and β-catenin expression in kidney tissues and ameliorated diabetes-induced kidney injury in rats.

The Active Compounds and Therapeutic Target of Tripterygium wilfordii Hook. f. in Attenuating Proteinuria in Diabetic Nephropathy: A Review

“…Wnt/β-catenin signaling is an evolutionary conserved signaling pathway, which plays a core role in modulating kidney injury and repair ( 114 ). In DN rats, Chang et al drew a conclusion that TWHF mitigates hyperglycemia-induced upregulated Wnt-1 and β-catenin expression in kidney tissues and ameliorates kidney injury ( 67 ) ( Table 1 , Figures 2 , 3 ).…”

Combination of Ginsenoside Rg1 and Astragaloside IV reduces oxidative stress and inhibits TGF-&beta;1/Smads signaling cascade on renal fibrosis in rats with diabetic nephropathy

“… 6 , 7 Many results have shown that TGF-β expression is upregulated in animal renal fibrosis models as well as human counterparts. 8 , 9 The transition of renal tubular epithelial cells to myofibroblasts which synthesize excessive amounts of extracellular matrix thus leading to renal fibrosis is modulated by TGF-β through TGF-β/Smads signaling pathway. 2 Furthermore, oxidative stress and TGF-β/Smads signaling together with other disease processes interactively and rapidly promote DN.…”

Shenning II Decoction Inhibits Epithelial-Mesenchymal Transition of Renal Tubular Epithelial Cells via Regulation of Wnt/&lt;i&gt;β&lt;/i&gt;-Catenin Signaling

“…Likewise, serum and urine levels of the EMT markers MMP-2 and -9 and E-cadherin were found to be elevated in CKD children [13]. Expression of interstitial cell markers has also been observed in the renal tubules of patients with diabetic nephropathy [14], lupus nephritis [15], oligoimmune complex type crescentic glomerulonephritis [16], IgA nephropathy [17], and chronic allograft nephropathy [18]. Thus, renal tubular EMT is an important mechanism of renal fibrosis and progression.…”