Notoginsenoside R1 ameliorates podocyte adhesion under diabetic condition through α 3 β 1 integrin upregulation in vitro and in vivo

Abstract

Background: Decreased expression of α 3 β 1 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 α 3 β 1 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 α 3 β 1 integrin expression were measured in vitro and in vivo. Results: HG decreased podocyte adhesive capacity and α 3 β 1 integrin expression, the main podocyte anchoring dimer to the GBM. However, NR1 ameliorated impaired podocyte adhesive capacity and partially restored α 3 β 1 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 α 3 β 1 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 α 3 β 1 integrin upregulation. These findings might provide a potential new therapeutic option for the treatment of DKD.