Astragaloside IV (AST) is the major active saponin in Astragalus membranaceus and, reportedly, has a variety of pharmacological activities. However, the potential of AST to ameliorate high glucose-mediated renal tubular epithelial-mesenchymal transition (EMT) remains undetermined. The aim of the present research was to explore the effect and mechanism of AST in EMT of renal tubular epithelial cells, as an underlying mechanism of renal fibrosis and a vital feature involved in diabetic nephropathy. The effect of AST on the EMT of renal tubular epithelial cells (HK-2) stimulated by high glucose was investigated and it was attempted to elucidate the potential underlying mechanism. The expression of E-cadherin and -smooth muscle actin were determined by western blotting and immunofluorescence assays. The expression of the mammalian target of rapamycin complex 1 (mTORC1)/ ribosomal protein S6 kinase -1 (p70S6K) signaling pathway and protein levels of four transcriptional factors (snail, slug, twist and zinc finger E-box-binding homeobox 1) were also determined by western blotting. Additionally, extracellular matrix components, including fibronectin (FN) and collagen type IV (Col IV) were detected by ELISA. The results suggested that the EMT of HK-2 cells and the mTORC1/p70S6K pathway were activated by high glucose. The expression of snail and twist in HK-2 cells was elevated by high glucose. Furthermore, extracellular matrix components, FN and Col IV, were increased in HK-2 cells cultured with high glucose. In turn, treatment with AST reduced EMT features in HK-2 cells, inhibited mTORC1/p70S6K pathway activation, downregulated expression of snail and twist, and reduced secretion of FN and Col IV. In summary, the findings suggested that AST ameliorates high glucose-mediated renal tubular EMT by blocking the mTORC1/p70S6K signaling pathway in HK-2 cells.
[1]Peoples Hosp Jiangyin, Dept Pharm, 163 Shoushan Rd, Jiangyin 214400, Jiangsu, Peoples R China;
[2]Xuzhou Med Univ, Jiangsu Key Lab New Drug Res & Clin Pharm, Xuzhou 221004, Jiangsu, Peoples R China;
[3]Southern Med Univ, Dept Pharm, Shenzhen Hosp, Shenzhen 518000, Guangdong, Peoples R China;
[4]Fudan Univ, Childrens Hosp, Dept Pharm, 399 Wanyuan Rd, Shanghai 201102, Peoples R China
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