Role of the Wnt/β-catenin signaling pathway in inducing apoptosis and renal fibrosis in 5/6-nephrectomized rats

摘要

Renal fibrosis is the final common pathway of all progressive renal disease. Excessive and chronic activation of the Wnt/β-catenin signaling pathway results in chronic kidney disease (CKD) progression. To mimic CKD, the present study used 5/6-nephrectomized rats, and alterations in kidney histology, expression of β-catenin and renal cell apoptosis were assessed. In addition, mesangial cells were cultured in vitro and transfected with β-catenin siRNA to evaluate the effect of blocking Wnt/β-catenin signaling on cell apoptosis and the expression of markers of renal fibrosis. The results demonstrated that CKD rat kidney tissues exhibited moderate renal fibrosis and significantly increased expression levels of β-catenin and apoptosis associated proteins compared with sham-operated rats. In vitro, silencing of β-catenin by siRNA attenuated tumor necrosis factor-α-induced apoptosis and decreased mRNA expression levels of various markers of fibrosis, including fibronectin, transforming growth factor-β, and collagen I, III and IV. In conclusion, inhibition of Wnt/β-catenin signaling by β-catenin silencing attenuated apoptosis and expression of fibrosis-associated markers in renal cells. The present study suggested that the Wnt/β-catenin signaling pathway may serve as a potential treatment strategy for renal fibrotic disorders.