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Mol Cell Endocrinol. 2014 Mar 25;384(1-2):109-16. doi: 10.1016/j.mce.2014.01.022. Epub 2014 Feb 5.

Berberine attenuates high glucose-induced proliferation and extracellular matrix accumulation in mesangial cells: involvement of suppression of cell cycle progression and NF-κB/AP-1 pathways.

Author information

1
Laboratory of Pharmacology & Toxicology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China; Vascular Biology Research Institute, Guangdong Pharmaceutical University, Guangzhou 510006, China.
2
Vascular Biology Research Institute, Guangdong Pharmaceutical University, Guangzhou 510006, China.
3
Laboratory of Pharmacology & Toxicology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
4
Department of Cancer, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou 510006, China.
5
Vascular Biology Research Institute, Guangdong Pharmaceutical University, Guangzhou 510006, China. Electronic address: wanglijing62@163.com.
6
Laboratory of Pharmacology & Toxicology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China. Electronic address: huangheq@mail.sysu.edu.cn.

Abstract

Berberine has been shown to have renoprotective effects on diabetes through attenuating TGF-β1 and fibronectin (FN) expression. However, how berberine regulates TGF-β1 and FN is not fully clear. Here we investigated whether berberine inhibited TGF-β1 and FN expression in high glucose-cultured mesangial cells. Berberine significantly inhibited mesangial cell proliferation and hypertrophy by increasing the cell population in G1-phase and reducing that in S-phase. In addition, berberine reversed high glucose-induced down-regulation of cyclin-dependent kinase inhibitor p21(Waf1)/(Cip1) and p27(Kip1). Berberine inhibited p65 translocation to the nucleus and c-jun phosphorylation induced by high glucose. Furthermore, berberine attenuated high glucose-induced expression of TGF-β1 and FN. Using a luciferase reporter assay, we found that high glucose-induced transcription activity of NF-κB and AP-1 was blocked by berberine. Electrophoretic mobility shift assay showed that high glucose increased that NF-κB and AP-1 DNA binding activity. These data indicate that berberine inhibited mesangial cell proliferation and hypertrophy by modulating cell cycle progress. In addition, berberine suppressed high glucose-induced TGF-β1 and FN expression by blocking NF-κB/AP-1 pathways.

KEYWORDS:

AP-1; Berberine; Cell cycle; High glucose; Mesangial cells; NF-κB

PMID:
24508662
DOI:
10.1016/j.mce.2014.01.022
[Indexed for MEDLINE]

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