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

Berberine has been shown to have renoprotective effects on diabetes through attenuating TGF-beta 1 and fibronectin (FN) expression. However, how berberine regulates and FN is not fully clear. Here we investigated whether berberine inhibited TGF-beta 1 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 glucoseinduced 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-beta 1 and FN. Using a luciferase reporter assay, we found that high glucose-induced transcription activity of NF-kappa B and AP-1 was blocked by berberine. Electrophoretic mobility shift assay showed that high glucose increased that NF-kappa B 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-beta 1 and FN expression by blocking NF-kappa B/AP-1 pathways. (C) 2014 Elsevier Ireland Ltd. All rights reserved.