Notoginsenoside R1 Ameliorates Podocyte Adhesion Under Diabetic Condition Through alpha(3)beta(1) Integrin Upregulation in Vitro and in Vivo

作者：Gui, Dingkun; Wei, Li^*; Jian, Guihua; Guo, Yongping; Yang, Jiajun; Wang, Niansong

来源：Cellular Physiology and Biochemistry, 2014, 34(6): 1849-1862.

DOI：10.1159/000366384

• Notoginsenoside R1
• Podocyte adhesion
• Oxidative stress
• alpha(3)beta(1) integrin
• Diabetic condition

Background: Decreased expression of alpha(3)beta(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 alpha(3)beta(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 100 mu g / ml of NR1 for 24 h. Podocyte adhesion, albuminuria, oxidative markers, renal histopathology, podocyte number per glomerular volume, integrin-linked kinase (ILK) activity and alpha(3)beta(1) integrin expression were measured in vitro and in vivo. Results: HG decreased podocyte adhesive capacity and alpha(3)beta(1) integrin expression, the main podocyte anchoring dimer to the GBM. However, NR1 ameliorated impaired podocyte adhesive capacity and partially restored alpha(3)beta(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 alpha(3)beta(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 alpha(3)beta(1) integrin upregulation. These findings might provide a potential new therapeutic option for the treatment of DKD.

• 出版日期2014
• 单位上海交通大学