Astragaloside IV ameliorates high glucose‑induced renal tubular epithelial‑mesenchymal transition by blocking mTORC1/p70S6K signaling in HK‑2 cells

Abstract

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 α-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 β-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.

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“…Astragaloside (Gao et al, 2012;Gui et al, 2013;Wang et al, 2014;Xu et al, 2014a;Che et al, 2015;Wang et al, 2015d;Zhou et al, 2017b;Chen et al, 2018;Du et al, 2018;Ji et al, 2018;Chen et al, 2019b;Ju et al, 2019;Qu et al, 2019;Su et al, 2019;Wang et al, 2019c), calycosin (Tang et al, 2011; Tripterygium glycoside (Wan et al, 2010;Cheng et al, 2015a;Ma et al, 2015b;Wu et al, 2017;Gong et al, 2018;Zhan et al, 2019;Wang et al, 2020), triptolide (Gao et al, 2010;Yuan et al, 2011;Ma et al, 2013;Cao et al, 2015;Zhou et al, 2016;Dong et al, 2017;Li et al, 2017c;Liang et al, 2018;Yang et al, 2019b;Wan et al, 2020), celastrol (Yu et al, 2018;Zhang et al, 2019c) Puerarin (Kim et al, 2010;Zhong et al, 2014;Pan et al, 2015;Song et al, 2016;Zhou et a...…”