Benazepril Promotes the Proliferation and Differentiation of Urine-Derived Stem Cells from Children with Nephrotic Syndrome During the Chronic Kidney Disease Stage.

Abstract

Nephrotic Syndrome (NS), especially in the Chronic Kidney Disease (CKD) stage, poses significant challenges in pediatric nephrology. Urine-derived stem cells (USCs) show promise for renal repair and regeneration. While benazepril is commonly used to treat CKD, its impact on USCs from children with NS during the CKD stage is unclear. USCs were isolated from the urine of 6 healthy children and 6 with NS (CKD stage), cultured through passages, and their morphology and cell surface markers were assessed microscopically and by flow cytometry, respectively. USCs were treated with benazepril at concentrations of 1, 10, 20, 40 μmol/L, and proliferation was evaluated using the CCK-8 assay. ROS levels were measured using DCFH-DA probe, and the expression levels of IL-1β, Connexin 43, AEC, ACE2, Ang2, AQP-1 and E-cadherin were analyzed by Western Blot. Tubular epithelial cell differentiation was also examined. USCs could be cultured from both healthy and NS (CKD stage) children, but USCs from NS children only reached passage 5 and exhibited weaker proliferation and differentiation abilities compared to those from healthy children. IL-1β, Connexin 43, ROS,ACE and Ang2 levels were higher in USCs from NS children than in those from healthy children, while ACE2 showed the opposite trend. Treatment with 1 μmol/L benazepril enhanced the proliferation and differentiation ability of USCs from NS children, inhibiting the level of inflammation factors, ROS, ACE and Ang2 while promoting ACE2 expression in these cells. This study offers valuable insights for future USCs applications.