Minnelide combined with Angptl3 knockout completely protects mice with adriamycin nephropathy via suppression of TGF-β1-Smad2 and p53 pathways

• DOI: 10.1016/j.intimp.2022.109656
• Publication Date: 2023-01-04T05:52:11Z
• Authors: Baowei Ji; Junchao Liu; Yanli Ma; Ye Yin; Hong Xu; Qian Shen; Jian Yu
• Keywords: Nephrin; Podocin; Knockout mouse; Triptolide; Gene knockout

Minimal change disease (MCD) is the common type of nephrotic syndrome in children. There 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) closely related renal Angptl3 knockout significantly alleviated proteinuria mice with adriamycin nephropathy (AN), however, some was still present. Minnelide a water-soluble prodrug triptolide which has been used for glomerular diseases. Therefore, this study aimed investigate whether minnelide, combined knockout, could completely protect AN its mechanism. induced B6;129S5 female by tail vein injection 25 mg/kg Adriamycin (ADR), 200 ug/kg/d minnelide. The results showed minnelide reduced restored foot processes AN. Moreover, AN, distribution nephrin, podocin cd2ap inflammatory factors (Tumor necrosis factor alpha (TNF-α), Interleukin-6 (IL-6) Interleukin-1β (IL-1β)). Through RNA sequencing experiments, we ameliorate fibrosis apoptosis inhibiting TGF-β1-Smad2 p53 pathways respectively. In primary podocytes, alleviates ADR-induced decreases cd2ap, upregulation Bax downregulation Bcl-2. Overall, our shows protects TGF-β1-smad2 pathways.