Notoginsenoside R1 Ameliorates Podocyte Adhesion Under Diabetic Condition Through a₃�₁Integrin Upregulationin Vitroandin 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.

Notoginsenoside R1 Protects against Neonatal Cerebral Hypoxic-Ischemic Injury through Estrogen Receptor-Dependent Activation of Endoplasmic Reticulum Stress Pathways

“…10 and 11). NGR1 is an estrogen receptor agonist (Sun et al, 2013;Gui et al, 2014) that can regulate the Nuclear factor kB (NF-kB) (Zhong L et al, 2015) or autophagy (Lu et al, 2011;Zhou et al, 2014) via estrogen receptor under the pathologic circumstance. In neuronal ischemia, NGR1 action on ERa and ERb as an agonist to strengthen the role of ERa and ERb then attenuates the ER stress.…”

“…NGR1 is a phytoestrogen that has been used in treatment of cardiac dysfunction (Sun et al, 2013), diabetic kidney disease (Gui et al, 2014), and acute liver failure . NGR1 can regulate Akt/Nrf2 pathways or tumor necrosis factor-a via estrogen receptor under the pathologic circumstance Zhong et al, 2015).…”

Notoginsenoside R1 attenuates glucose-induced podocyte injury via the inhibition of apoptosis and the activation of autophagy through the PI3K/Akt/mTOR signaling pathway

“…It has been demonstrated that NR1 attenuates renal ischemia-reperfusion injury in rats (12). It has also been demonstrated that NR1 attenuates the glucose-induced impairement of podocyte adhesive capacity and subsequent podocyte depopulation in rats through the upregulation of α3β1 integrin (13). However, it is not clear whether NR1 has any effect on the number of podocytes by affecting apoptosis and inducing autophagy and podocyte integrity in addition to its effect on podocyte adhesion (13).…”

Mechanistic Insight and Management of Diabetic Nephropathy: Recent Progress and Future Perspective

“…Nowadays, an increasing understanding and popularity of TCM caused great interests in lots of diseases on its efficiency and mechanisms by the spring up of molecular biology, especially the application of Ultra Performance Liquid Chromatography (UPLC) and mass spectrometer which could analyze the active ingredients of TCM and manifest herbal medicine as western medicine. For the past few years, notoginsenoside R1 could retard DN by ameliorating podocyte adhesion through α 3 β 1 integrin upregulation and astragaloside IV could inhibit podocyte apoptosis by downregulation of PERK-ATF4-CHOP pathway [71, 72]. Furthermore, there is a present study that aimed to evaluate the effect of ARB combined with Chinese formula Qidan Dihuang Grain (QDDHG) in improving proteinuria of patients of DN [73].…”