Minimal change disease (MCD) is the common type of nephrotic syndrome in children. There is an urgent need to explore new treatment methods as current treatments have many drawbacks and cause significant side effects. Our group found that Angiopoietin-like protein 3 (Angptl3) is closely related to renal disease and Angptl3 knockout significantly alleviated proteinuria in mice with adriamycin nephropathy (AN), however, some proteinuria was still present. Minnelide is a water-soluble prodrug of triptolide which has been used for the treatment of glomerular diseases. Therefore, this study aimed to investigate whether minnelide, combined with Angptl3 knockout, could completely protect mice with AN and its mechanism. AN was induced in B6;129S5 female mice by tail vein injection of 25?mg/kg of Adriamycin (ADR), and treatment with 200 ug/kg/d of minnelide. The results showed that minnelide combined with Angptl3 knockout completely reduced proteinuria and restored the foot processes in mice with AN. Moreover, in Angptl3 knockout mice with AN, minnelide restored the distribution of nephrin, podocin and cd2ap and reduced inflammatory factors (Tumor necrosis factor alpha (TNF-α), Interleukin-6 (IL-6) and Interleukin-1β (IL-1β)). Through RNA sequencing and related experiments, we found minnelide could ameliorate fibrosis and apoptosis by inhibiting TGF-β1-Smad2 and p53 pathways in Angptl3 knockout mice with AN, respectively. In Angptl3 knockout primary podocytes, triptolide alleviates ADR-induced decreases in nephrin, podocin and cd2ap, upregulation of Bax and downregulation of Bcl-2. Overall, our study shows that minnelide combined with Angptl3 knockout completely protects mice with AN by inhibiting the TGF-β1-smad2 and p53 pathways.
文章引用产品列表
-
- EK282
- ELISA试剂盒
Mouse TNF-a ELISA Kit检测试剂盒(酶联免疫吸附法)
- ¥1,600.00 – ¥10,800.00
-
- EK282HS
- ELISA试剂盒, 高敏试剂盒
Mouse TNF-α High Sensitivity ELISA Kit检测试剂盒(酶联免疫吸附法)
- ¥2,000.00 – ¥3,400.00
-
- EK206
- ELISA试剂盒
Mouse IL-6 ELISA Kit检测试剂盒(酶联免疫吸附法)
- ¥1,600.00 – ¥10,800.00
-
- EK206HS
- ELISA试剂盒, 高敏试剂盒
Mouse IL-6 High Sensitivity ELISA Kit检测试剂盒(酶联免疫吸附法)
- ¥2,000.00 – ¥3,400.00
-
- EK201BHS
- ELISA试剂盒, 高敏试剂盒
Mouse IL-1β High Sensitivity ELISA Kit检测试剂盒(酶联免疫吸附法)
- ¥2,000.00 – ¥3,400.00
-
- EK201B
- ELISA试剂盒
Mouse IL-1β ELISA Kit 检测试剂盒(酶联免疫吸附法)
- ¥1,600.00 – ¥10,800.00