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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

View Article: PubMed Central - PubMed

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.

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Effects of berberine on albuminuria in diabetic nephropathy model KKAy mice.Notes: Data are presented as the mean ± standard deviation. **P<0.01 compared with the NG and ##P<0.01.Abbreviations: MG, model group; NG, normal control group; TG, treatment group.
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f2-dddt-11-1065: Effects of berberine on albuminuria in diabetic nephropathy model KKAy mice.Notes: Data are presented as the mean ± standard deviation. **P<0.01 compared with the NG and ##P<0.01.Abbreviations: MG, model group; NG, normal control group; TG, treatment group.

Mentions: Similar to the body weight, 24 h urine protein was detected every 4 weeks (Table 3; Figure 2). As time progressed, the 24 h urine protein of the MG increased gradually, and it was significantly higher than that of the C57BL/6J mice in the control group at 14 weeks (P<0.01). Relative to the MG, the 24 h urinary protein in the BBR group was significantly decreased (P<0.01). Although there was an increase in urinary protein content during the 22nd and the 26th weeks, the mean urinary protein content in the TG of mice was significantly lower than that in the MG, as evidenced by measurements taken at 18, 22, and 26 weeks (P<0.01), and the growth rate was significantly decreased relative to the MG. The above data clearly indicate that BBR can delay the progression of renal dysfunction and protect the renal function.


Effect of berberine on the renal tubular epithelial-to-mesenchymal transition by inhibition of the Notch/snail pathway in diabetic nephropathy model KKAy mice
Effects of berberine on albuminuria in diabetic nephropathy model KKAy mice.Notes: Data are presented as the mean ± standard deviation. **P<0.01 compared with the NG and ##P<0.01.Abbreviations: MG, model group; NG, normal control group; TG, treatment group.
© Copyright Policy
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC5384688&req=5

f2-dddt-11-1065: Effects of berberine on albuminuria in diabetic nephropathy model KKAy mice.Notes: Data are presented as the mean ± standard deviation. **P<0.01 compared with the NG and ##P<0.01.Abbreviations: MG, model group; NG, normal control group; TG, treatment group.
Mentions: Similar to the body weight, 24 h urine protein was detected every 4 weeks (Table 3; Figure 2). As time progressed, the 24 h urine protein of the MG increased gradually, and it was significantly higher than that of the C57BL/6J mice in the control group at 14 weeks (P<0.01). Relative to the MG, the 24 h urinary protein in the BBR group was significantly decreased (P<0.01). Although there was an increase in urinary protein content during the 22nd and the 26th weeks, the mean urinary protein content in the TG of mice was significantly lower than that in the MG, as evidenced by measurements taken at 18, 22, and 26 weeks (P<0.01), and the growth rate was significantly decreased relative to the MG. The above data clearly indicate that BBR can delay the progression of renal dysfunction and protect the renal function.

View Article: PubMed Central - PubMed

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 &alpha;-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.

No MeSH data available.


Related in: MedlinePlus