Shenning II Decoction Inhibits Epithelial-Mesenchymal Transition of Renal Tubular Epithelial Cells via Regulation of Wnt/<i>β</i>-Catenin Signaling

• 作者: Fengfeng Ge Houcai Huang Liming Fang Meixiao Sheng Shengfang Xie Wei Zhang Yuanzhang Yao
• 来源期刊: 肾脏病(英文)
• 学科: 医学
• 关键词: Chronic Kidney Disease Renal Fibrosis Wnt/Beta-Catenin Signaling Pathway EMT Traditional Chinese Medicine
• 年，卷（期）: 2020,（4）
• 页码范围: 323-337
• 页数: 15页
• 分类号: R73

摘要

This study was conducted to investigate the effect of Shenning II decoction on renal function, renal pathology, epithelial-to-mesenchymal transition (EMT), and Wnt/beta-catenin signaling in unilateral ureteral obstruction (UUO) renal fibrosis. Sprague-Dawley rats were randomly divided into blank control, sham-operated, UUO model (untreated), and UUO with Shenning decoction treatment (high, medium, and low dose) groups. Renal function was evaluated based on blood urea nitrogen (BUN) and serum creatinine (Scr) levels. Histopathological analysis of rat kidney tubular tissue was carried out and E-cadherin, fibronectin, vimentin, Wnt4, glycogen synthase kinase (GSK)<i>β</i>, low-density lipoprotein receptor-related protein (LRP)5, LRP6, <i>β</i>-catenin, Snail, and fibroblast-specific protein (FSP)1 expression was evaluated by immunohistochemistry, western blotting, and real-time PCR. BUN and Scr were found to be increased in UUO when compared with the sham rats (P < 0.05), but this was reversed (albeit non-significantly) in rats treated with high and medium doses of Shenning II (P > 0.05). Shenning II decoction decreased histopathological scores relative to the UUO rats (P < 0.05). Protein expression of E-cadherin was increased, whereas that of vimentin, Wnt4, <i>β</i>-catenin, and fibronectin was decreased in Shenning I-treated rats, when compared with the untreated UUO rats, as determined by immunohistochemistry and western blotting (P < 0.05). Wnt4, <i>β</i>-catenin, GSK-3<i>β</i>, LRP5, LRP6, Snail, and FSP1 mRNA levels were also downregulated by Shenning II decoction treatment (P < 0.05). Shenning II decoction, therefore, protects against renal fibrosis by blocking renal tubular EMT via suppression of Wnt/beta-catenin signaling.