ROS induces epithelial‑mesenchymal transition via the TGF‑β1/PI3K/Akt/mTOR pathway in diabetic nephropathy

Lu,Qian; Wang,Wen‑Wen; Zhang,Ming‑Zhu; Ma,Zhong‑Xuan; Qiu,Xin‑Ran; Shen,Mengli; Yin,Xiao‑Xing

doi:10.3892/etm.2018.7014

ROS induces epithelial‑mesenchymal transition via the TGF‑β1/PI3K/Akt/mTOR pathway in diabetic nephropathy

Authors:
- Qian Lu
- Wen‑Wen Wang
- Ming‑Zhu Zhang
- Zhong‑Xuan Ma
- Xin‑Ran Qiu
- Mengli Shen
- Xiao‑Xing Yin
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Affiliations: Department of Pharmacy, Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, Jiangsu 221004, P.R. China, Department of Pharmacy, Wuxi Higher Health Vocational Technology School, Wuxi, Jiangsu 214000, P.R. China, Deparment of Clinical Pharmacy, Changzhou Fourth People's Hospital, Changzhou, Jiangsu 213000, P.R. China
Published online on: November 26, 2018 https://doi.org/10.3892/etm.2018.7014
Pages: 835-846

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Abstract

Oxidative stress has been reported to serve an important role in the development and progression of diabetic nephropathy (DN). Epithelial‑mesenchymal transition (EMT) of renal tubular epithelial cells promotes renal fibrosis in DN, while the mechanism of reactive oxygen species (ROS)‑mediated EMT is not fully understood. The aim of the present study was to investigate the effect of high glucose‑induced ROS on the activation of the transforming growth factor (TGF)‑β1/phosphoinositide 3 kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway in a normal rat kidney tubular epithelial cell line (NRK‑52E) and rats with type 1 diabetes. In vitro, high glucose-stimulated ROS production resulted in increased TGF‑β1 expression as well as an increase in the Akt and mTOR phosphorylation ratio, resulting in EMT. When cells were pre‑treated with ROS inhibitors, changes in TGF‑β1, Akt and mTOR were significantly ameliorated. In vivo, diabetic rats experienced a significant decline in renal function and severe renal fibrosis compared with control rats at 8 weeks following streptozocin injection. Levels of malondialdehyde and TGF‑β1/PI3K/Akt/mTOR pathway activation were increased in the renal cortex of rats with diabetes compared with the control rats. Furthermore, renal fibrosis was further aggravated in DN compared with the control rats. The results of the present study suggest that ROS serves an important role in mediating high glucose‑induced EMT and inhibits activation of the TGF‑β1/PI3K/Akt/mTOR pathway. ROS may therefore have potential as a treatment approach to prevent renal fibrosis in DN.

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