Gliquidone improves retinal injury to relieve diabetic retinopathy via regulation of SIRT1/Notch1 pathway

Mengdan Yu,Lijun Zhang,Zhenhua Zhang,Shasha Sun

doi:10.1186/s12886-021-02215-8

Mengdan Yu, Lijun Zhang + Show 2 more

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https://doi.org/10.1186/s12886-021-02215-8

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Abstract

BackgroundDiabetic retinopathy (DR) is a common and potentially devastating microvascular complication of diabetes mellitus (DM). The main features of DR are inflammation and oxidative damage. Gliquidone (GLI) is confirmed to be a hypoglycemic drug by oral administration. The current study is aimed to investigate the role and mechanism of GLI on the pathogenesis of DR.MethodsHigh glucose (HG)-induced human retinal endothelial cells (HRECs) were used to explore the anti-inflammatory and anti-oxidant effects of GLI on DR in vitro. Streptozotocin (STZ)-induced DM rats were used to investigate the effects of GLI on retinal structures, inflammation, and oxidative stress. The levels of SIRT1/Notch1 pathway-related proteins were determined by western blotting.ResultsGLI treatment promoted the viability and inhibited the apoptosis of HG-induced HRECs. Meanwhile, the levels of interleukin (IL)-6, IL-1β, tumour necrosis factor alpha and reactive oxygen species were suppressed, while both catalase and superoxide dismutase were elevated after GLI treatment in HG-induced HRECs. Furthermore, we found that Silencing information regulator 2 related enzyme 1 (SIRT1) silencing reversed the inhibiting effects of GLI on the levels of protein Notch1 and effector genes Hes1 and Hey2. Similar anti-inflammatory and anti-oxidant effects of GLI in STZ-induced DM rats were observed. Additionally, GLI administration also repressed vascular hyperpermeability in vivo.ConclusionGLI may be an effective agent to improve DR through repression of inflammation and oxidative stress via SIRT1/Notch1 pathway.

Highlights

Diabetic retinopathy (DR) is a common and potentially devastating microvascular complication of diabetes mellitus (DM)
As illustrated in Fig. 1AC, we found that compared to the normal glucose (NG) groups, High glucose (HG) treatment significantly increased the contents of glucose, triglyceride, and 2DG6P in human retinal endothelial cells (HRECs) (P < 0.01), suggesting that a DM cell model was successfully established
Analysis for inflammation, oxidative stress and vascular endothelial growth factor (VEGF) level According to the manufacturer’s instructions, the levels of interleukin (IL)-6, IL-1β, tumour necrosis factor alpha (TNF-)α, reactive oxygen species (ROS), CAT, superoxide dismutase (SOD), and VEGF in retina tissues of DM rats and/or HG-induced HRECs were measured by the corresponding commercial kits

Summary

Introduction

Diabetic retinopathy (DR) is a common and potentially devastating microvascular complication of diabetes mellitus (DM). Ji et al conducted a DR rat model and demonstrated a decreased expression of SIRT1 in high glucose-induced rat retinal endothelial cells (RRECs) and retinal tissues of DR rats [16]. They further indicated that overexpressed SIRT1 can accelerate the proliferation of RRECs [16]. Tian et al constructed a diabetic nephropathy (DN) mouse model and showed that GLI may improve oxidative damage and renal interstitial fibrosis to delay the progression of DN through inhibiting Notch signaling [25]. Whether GLI interacts with SIRT1/ Notch pathway to affect DR progression is still unclear

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