Emodin attenuates high glucose-induced TGF-β1 and fibronectin expression in mesangial cells through inhibition of NF-κB pathway

Abstract

The activation of nuclear factor-κB (NF-κB) and the subsequent overexpression of its downstream targets transforming growth factor-β1 (TGF-β1) and fibronectin (FN) are among the hallmarks for the progressive diabetic nephropathy. Our previous studies demonstrated that emodin ameliorated renal injury and inhibited extracellular matrix accumulation in kidney and mesangial cells under diabetic condition. However, the molecular mechanism has not been fully elucidated. Here, we showed that emodin significantly attenuated high glucose-induced NF-κB nuclear translocation in mesangial cells. Interestingly, emodin also inhibited the DNA-binding activity and transcriptional activity of NF-κB. Furthermore, NF-κB-mediated TGF-β1 and FN expression was significantly decreased by emodin. These results demonstrated that emodin suppressed TGF-β1 and FN overexpression through inhibition of NF-κB activation, suggesting that emodin-mediated inhibition of the NF-κB pathway could protect against diabetic nephropathy.

Keywords: DMEM; Dulbecco's modified Eagle's medium; ECM; EMSA; Emodin; FN; High glucose; MCs; Mesangial cells; NF-κB; TGF-β1; electrophoretic mobility shift assay; extracellular matrix; fibronectin; mesangial cells; nuclear factor-κB; transforming growth factor-β1.