Notoginsenoside R1 Ameliorates Podocyte Adhesion Under Diabetic Condition Through α3β1 Integrin Upregulation in Vitro and in Vivo

Abstract

Background: Decreased expression of α₃β₁ integrin may contribute to reduction in podocyte adhesion to glomerular basement membrane (GBM), which represents a novel early mechanism leading to diabetic kidney disease (DKD). Here, we examined the protective effects of Notoginsenoside R1 (NR1) on podocyte adhesion and α₃β₁ integrin expression under diabetic condition in vitro and in vivo. Methods: Conditionally immortalized mouse podocytes were exposed to high glucose (HG) with 10 and 100μg /ml of NR1 for 24 h. Podocyte adhesion, albuminuria, oxidative markers, renal histopathology, podocyte number per glomerular volume, integrin-linked kinase (ILK) activity and α₃β₁ integrin expression were measured in vitro and in vivo. Results: HG decreased podocyte adhesive capacity and α₃β₁ integrin expression, the main podocyte anchoring dimer to the GBM. However, NR1 ameliorated impaired podocyte adhesive capacity and partially restored α₃β₁ integrin protein and mRNA expression. These in vitro observations were confirmed in vivo. In streptozotocin(STZ)-induced diabetic rats, treatment with NR1 (5 and 10 mg· kg^-1· d^-1) for 12 weeks partially restored the number of podocytes per glomerular volume and glomerular α₃β₁ integrin expression, as well as ameliorated albuminuria, histopathology and oxidative stress. NR1 also inhibited glomerular ILK activity in diabetic rats. Conclusion: NR1, a novel antioxidant, ameliorated glucose-induced impaired podocyte adhesive capacity and subsequent podocyte depopulation partly through α₃β₁ integrin upregulation. These findings might provide a potential new therapeutic option for the treatment of DKD.