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Effect of berberine on the renal tubular epithelial-to-mesenchymal transition by inhibition of the Notch/snail pathway in diabetic nephropathy model KKAy mice

Authors Yang GN, Zhao ZJ, Zhang XX, Wu AM, Huang YW, Miao YH, Yang MJ

Received 18 October 2016

Accepted for publication 28 February 2017

Published 31 March 2017 Volume 2017:11 Pages 1065—1079

DOI https://doi.org/10.2147/DDDT.S124971

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Ashok Kumar Pandurangan

Peer reviewer comments 3

Editor who approved publication: Dr James Janetka

Guannan Yang, Zongjiang Zhao, Xinxue Zhang, Amin Wu, Yawei Huang, Yonghui Miao, Meijuan Yang

School of Basic Medical Science, Beijing University of Chinese Medicine, Beijing, People’s Republic of China

Abstract: Renal tubular epithelial-to-mesenchymal transition (EMT) and renal tubular interstitial fibrosis are the main pathological changes of diabetic nephropathy (DN), which is a common cause of end-stage renal disease. Previous studies have suggested that berberine (BBR) has antifibrotic effects in the kidney and can reduce apoptosis and inhibit the EMT of podocytes in DN. However, the effect of BBR on the renal tubular EMT in DN and its mechanisms of action are unknown. This study was performed to explore the effects of BBR on the renal tubular EMT and the molecular mechanisms of BBR in DN model KKAy mice and on the high glucose (HG)-induced EMT in mouse renal tubular epithelial cells. Our results showed that, relative to the model mice, the mice in the treatment group had an improved general state and reduced blood glucose and 24-h urinary protein levels. Degradation of renal function was ameliorated by BBR. We also observed the protective effects of BBR on renal structural changes, including normalization of an index of renal interstitial fibrosis and kidney weight/body weight. Moreover, BBR suppressed the activation of the Notch/snail pathway and upregulated the α-SMA and E-cadherin levels in DN model KKAy mice. BBR was further found to prevent HG-induced EMT events and to inhibit the HG-induced expression of Notch pathway members and snail1 in mouse renal tubular epithelial cells. Our findings indicate that BBR has a therapeutic effect on DN, including its inhibition of the renal tubular EMT and renal interstitial fibrosis. Furthermore, the BBR-mediated EMT inhibition occurs through Notch/snail pathway regulation.

Keywords: berberine, EMT, renal interstitial fibrosis, diabetic nephropathy, Notch/snail pathway

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