Department of Pharmacology, School of Pharmacy, Guangxi Medical University, Nanning, Guangxi, People's Republic of China.
Exp Cell Res. 2013 Dec 10;319(20):3182-9. doi: 10.1016/j.yexcr.2013.10.006. Epub 2013 Oct 15.
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.
核因子-κB（NF-κB）的激活及其下游靶基因转化生长因子-β1（TGF-β1）和纤维连接蛋白（FN）的过度表达是糖尿病肾病进展的特征之一。我们之前的研究表明，大黄素在糖尿病条件下可改善肾脏损伤并抑制肾脏和系膜细胞中细胞外基质的积累。然而，其分子机制尚未完全阐明。在这里，我们表明大黄素可显著减轻高糖诱导的系膜细胞中 NF-κB 的核易位。有趣的是，大黄素还抑制了 NF-κB 的 DNA 结合活性和转录活性。此外，大黄素显著降低了 NF-κB 介导的 TGF-β1 和 FN 的表达。这些结果表明，大黄素通过抑制 NF-κB 激活来抑制 TGF-β1 和 FN 的过度表达，提示大黄素介导的 NF-κB 通路抑制可能有助于预防糖尿病肾病。
