Yihui Chen1, Yan Wang2, Yaping Jiang1, Xiaoyan Zhang3, Minjie Sheng1. 1. Department of Ophthalmology, Yangpu Hospital, Tongji University School of Medicine, Shanghai 200090, China. 2. Department of Neurology, Shanghai General Hospital (Shanghai First People's Hospital), Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China. 3. Department of Ophthalmology, Huashan Hospital, Fudan University, Shanghai 200040, China.
Abstract
BACKGROUND: Hyperglycaemia-induced angiogenesis plays an important role in diabetic retinopathy (DR). This study aimed to investigate the role of sirtuin1 (Sirt1)/forkhead box O3 (FOXO3) pathway in the effects of high-glucose on human umbilical vein endothelial cells (HUVECs). METHODS: HUVECs were divided into normal control group (5 mM glucose), high glucose group (30 mM), 30 mM glucose + shsirt1 group, 30 mM glucose + Sirt1 over-expression group (30 mM + Sirt1), 30 mM glucose + Sirt1 agonist SRT group, 30 mM glucose + SRT + FOXO3 silencing group (30 mM + SRT + siFOXO3). Cell proliferation, migration, invasion and apoptosis were determined. RESULTS: High glucose treatment reduced the expression of Sirt1 and FOXO3 in HUVECs. However, Sirt1 over-expression or SRT attenuated the high-glucose-induced inhibition of HUVEC proliferation and migration as well as reduced their apoptosis. In contrast, Sirt1 silencing deteriorated the high-glucose induced inhibition of HUVEC proliferation and migration and further increased HUVEC apoptosis. FOXO3 expression increased with the increase in Sirt1 expression, which was accompanied by enhanced cellular functions. These were abolished after FOXO3 silencing. In addition, Sirt1/FOXO3 regulated HUVEC activities via peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α). CONCLUSIONS: Sirt1/FOXO3 pathway is essential for the survival of endothelial cells under high-glucose and plays an important role in the development of diabetes-induced retinal vascular endothelial injury.
BACKGROUND: Hyperglycaemia-induced angiogenesis plays an important role in diabetic retinopathy (DR). This study aimed to investigate the role of sirtuin1 (Sirt1)/forkhead box O3 (FOXO3) pathway in the effects of high-glucose on human umbilical vein endothelial cells (HUVECs). METHODS: HUVECs were divided into normal control group (5 mM glucose), high glucose group (30 mM), 30 mM glucose + shsirt1 group, 30 mM glucose + Sirt1 over-expression group (30 mM + Sirt1), 30 mM glucose + Sirt1 agonist SRT group, 30 mM glucose + SRT + FOXO3 silencing group (30 mM + SRT + siFOXO3). Cell proliferation, migration, invasion and apoptosis were determined. RESULTS: High glucose treatment reduced the expression of Sirt1 and FOXO3 in HUVECs. However, Sirt1 over-expression or SRT attenuated the high-glucose-induced inhibition of HUVEC proliferation and migration as well as reduced their apoptosis. In contrast, Sirt1 silencing deteriorated the high-glucose induced inhibition of HUVEC proliferation and migration and further increased HUVEC apoptosis. FOXO3 expression increased with the increase in Sirt1 expression, which was accompanied by enhanced cellular functions. These were abolished after FOXO3 silencing. In addition, Sirt1/FOXO3 regulated HUVEC activities via peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α). CONCLUSIONS: Sirt1/FOXO3 pathway is essential for the survival of endothelial cells under high-glucose and plays an important role in the development of diabetes-induced retinal vascular endothelial injury.
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