Abstract
Background Diabetic retinopathy (DR) is a serious microvascular complication of diabetes. This study demonstrates the antiangiogenic effects of scutellarin (SCU) on high glucose- and hypoxia-stimulated human retinal endothelial cells (HRECs) and on a diabetic rat model by oral administration. The antiangiogenic mechanisms of SCU in vitro and in vivo were investigated. Method HRECs were cultured in high glucose- (30 mM D-glucose) and hypoxia (cobalt chloride-treated)-stimulated diabetic condition to evaluate the antiangiogenic effects of SCU by CCK-8 test, cell migration experiment (wound healing and transwell), and tube formation experiment. A streptozotocin-induced type II diabetic rat model was established to measure the effects of oral administration of SCU on protecting retinal microvascular dysfunction by Doppler waveforms and HE staining. We further used western blot, luciferase reporter assay, and immunofluorescence staining to study the antiangiogenic mechanism of SCU. The protein levels of phospho-ERK, phospho-FAK, phospho-Src, VEGF, and PEDF were examined in HRECs and retina of diabetic rats. Result Our results indicated that SCU attenuated diabetes-induced HREC proliferation, migration, and tube formation and decreased neovascularization and resistive index in the retina of diabetic rats by oral administration. SCU suppressed the crosstalk of phospho-ERK, phospho-FAK, phospho-Src, and VEGF in vivo and in vitro. Conclusions These results suggested that SCU can be an oral drug to alleviate microvascular dysfunction of DR and exerts its antiangiogenic effects by inhibiting the expression of the crosstalk of VEGF, p-ERK, p-FAK, and p-Src.
Highlights
Diabetic retinopathy (DR), an important cause of permanent vision loss in working-age adults, is a serious microvascular complication of diabetes [1]
To prove that a hyperglycemia/hypoxia human retinal endothelial cells (HRECs) model was successfully established by treatment with D-glucose (30 mM) and CoCl2 (200 μm/l), glucose content, glucose uptake, and triglyceride content were measured in HRECs that were cultured in control medium, mannitol-supplemented medium, glucose/CoCl2-supplemented medium, and glucose/CoCl2+SCU-supplemented medium
The results indicated that the glucose content, glucose uptake, and triglyceride content of the HRECs in the glucose/CoCl2 group were higher than those in the control and osmotic control groups (Figures 1(a)–1(c)), which indicated that HRECs treated with D-glucose (30 mM) and CoCl2 (200 μm/l) successfully established a diabetic cell model in vitro
Summary
Diabetic retinopathy (DR), an important cause of permanent vision loss in working-age adults, is a serious microvascular complication of diabetes [1]. This study demonstrates the antiangiogenic effects of scutellarin (SCU) on high glucose- and hypoxia-stimulated human retinal endothelial cells (HRECs) and on a diabetic rat model by oral administration. A streptozotocin-induced type II diabetic rat model was established to measure the effects of oral administration of SCU on protecting retinal microvascular dysfunction by Doppler waveforms and HE staining. The protein levels of phospho-ERK, phospho-FAK, phospho-Src, VEGF, and PEDF were examined in HRECs and retina of diabetic rats. Our results indicated that SCU attenuated diabetes-induced HREC proliferation, migration, and tube formation and decreased neovascularization and resistive index in the retina of diabetic rats by oral administration. These results suggested that SCU can be an oral drug to alleviate microvascular dysfunction of DR and exerts its antiangiogenic effects by inhibiting the expression of the crosstalk of VEGF, p-ERK, p-FAK, and p-Src
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