波多辛
自噬
雷公藤
足细胞
免疫印迹
肾
化学
基因沉默
细胞凋亡
医学
内科学
下调和上调
药理学
内分泌学
尼福林
生物化学
糖苷
有机化学
基因
蛋白尿
作者
Huifang Zhan,Juan Jin,Shikai Liang,Li Zhao,Jianguang Gong,Qiang He
出处
期刊:PubMed
日期:2019-08-01
卷期号:34 (8): 943-952
被引量:7
摘要
Diabetic kidney disease (DKD), one of the most common causes of end-stage renal disease(ESRD), remains prevalent in many populations. Podocyte loss and apoptosis play a crucial role in the progression of DKD. Tripterygium glycoside (TG), a widely used Chinese herb, exerted comprehensive protective effects on preventing DKD progression. This study was performed to assess the podocyte protective effect of tripterygium glycoside on DKD by the potential role of activation of autophagy and downregulating β-arrestin-1.Tripterygium glycoside and small interfering RNA (siRNA) of β-arrestin-1 were added to 10% db/db mice high-glucose serum induced podocytes in vitro. Autophagic activity was evaluated by transmission electronic microscopy, immunofluorescence staining and western blot analysis. Apoptotic activity was evaluated by Annexin V-FITC/PI flow cytometric analysis. The levels of nephrin and podocin, a marker protein of podocytes, were examined using western blot analysis.Significantly ameliorated podocyte apoptosis, increased nephrin and podocin levels and inhibited expression of β-arrestin-1 were observed after pretreatment of tripterygium glycoside in DKD mouse serum treated podocytes. Significantly higher levels of autophagic activity were also observed. Silencing β-arrestin-1 upregulated autophagic activity and ameliorated podocyte apoptosis. Silencing β-arrestin-1 in combination with tripterygium glycoside enhanced the levels of LC3-II and LC3-II/LC3-I ratios and reduced the expression of p62. Finally, we observed a notable reduction in podocyte apoptotic rate in DKD serum + siRNA-β-arrestin-1 + TG group compared to DKD serum + siRNA-β-arrestin-1 group, and upregulated protein levels of nephrin and podocin compared to treatment with siRNA-β-arrestin-1 only.This study demonstrated that tripterygium glycoside provided protection against podocyte injury induced by high-glucose serum, and that this effect was mediated by the concomitant activation of autophagy and downregulation of β-arrestin-1.
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