大黄素通过抑制 EZH2 改善梗阻性肾病的肾小管间质纤维化。
Emodin ameliorates tubulointerstitial fibrosis in obstructed kidneys by inhibiting EZH2.
机构信息
Department of Nephrology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, TCM Institute of Kidney Disease, Shanghai University of Traditional Chinese Medicine, Key Laboratory of Liver and Kidney Diseases (Shanghai University of Traditional Chinese Medicine), Ministry of Education, Shanghai Key Laboratory of Traditional Chinese Clinical Medicine (14DZ2273200), Shanghai, China.
Department of Nephrology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, TCM Institute of Kidney Disease, Shanghai University of Traditional Chinese Medicine, Key Laboratory of Liver and Kidney Diseases (Shanghai University of Traditional Chinese Medicine), Ministry of Education, Shanghai Key Laboratory of Traditional Chinese Clinical Medicine (14DZ2273200), Shanghai, China.
出版信息
Biochem Biophys Res Commun. 2021 Jan 1;534:279-285. doi: 10.1016/j.bbrc.2020.11.094. Epub 2020 Dec 4.
Emodin, a major component of Chinese herbal rhubarb, delays the progression of chronic renal failure. However, the effect and working mechanisms of Emodin on renal tubulointerstitial fibrosis remains elusive. We hypothesized that emodin inhibits renal tubulointerstitial fibrosis through EZH2, a histone methyltransferase. Our in vivo and in vitro studies demonstrate that emodin reduced extracellular collagen deposition and inhibited Smad3 and CTGF pro-fibrotic signaling pathways, which were correlated with the down-regulation of EZH2 and reduced trimethylation of histone H3 on lysine 27 (H3k27me3) in NRK-49F fibrotic cells and UUO kidneys. Inhibition of EZH2 by 3-DZNeP blocked or attenuated the anti-fibrotic effect of emodin in UUO kidneys and NRK-49F cells. These data indicate that emodin inhibits renal tubulointerstitial fibrosis in obstructed kidneys and this effect is mediated through EZH2.
大黄素是中国草药大黄的主要成分，可延缓慢性肾衰竭的进展。然而，大黄素对肾小管间质纤维化的作用和作用机制仍不清楚。我们假设大黄素通过组蛋白甲基转移酶 EZH2 抑制肾间质纤维化。我们的体内和体外研究表明，大黄素减少细胞外胶原沉积，抑制 Smad3 和 CTGF 促纤维化信号通路，这与 EZH2 下调和组蛋白 H3 赖氨酸 27 上的三甲基化 (H3k27me3) 减少相关在 NRK-49F 纤维化细胞和 UUO 肾脏中。3-DZNeP 抑制 EZH2 可阻断或减弱大黄素在 UUO 肾脏和 NRK-49F 细胞中的抗纤维化作用。这些数据表明，大黄素抑制梗阻性肾脏中的肾小管间质纤维化，这种作用是通过 EZH2 介导的。
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