Abstract
Background G9a, a well-known methyltransferase, plays a vital role in biological processes. However, its role in corneal neovascularization (CoNV) remains unclear. Methods. In vitro and in vivo models were assessed in hypoxia-stimulated angiogenesis and in a mouse model of alkali burn-induced CoNV. Human umbilical vein endothelial cells (HUVECs) were cultured under hypoxic conditions and different reoxygenation times to identify the molecular mechanisms involved in this process. Results In this study, we found that G9a was positively related to corneal alkali burn-induced injury. Inhibition of G9a with BIX 01294 (BIX) alleviated corneal injury, including oxidative stress and neovascularization in vivo models were assessed in hypoxia-stimulated angiogenesis and in a mouse model of alkali burn-induced CoNV. Human umbilical vein endothelial cells (HUVECs) were cultured under hypoxic conditions and different reoxygenation times to identify the molecular mechanisms involved in this process.
Highlights
Angiogenesis is an essential biological process that plays a vital role in the tumorigenesis, diabetic retinopathy, and macular degeneration
The antibodies used in western blotting (WB) experiments, G9a, Nrf2, HO-1, NADPH oxidase 4 (Nox4), vascular endothelial growth factor (VEGF), cluster of differentiation 31 (CD31), CD34, and antiβ-actin antibodies were purchased from Abcam
The results indicated that cell viability decreased after H/R, but different concentrations of G9a inhibitor could elevate Human umbilical vein endothelial cells (HUVECs) cell proliferation, with more obvious effect observed at 10 μM
Summary
Angiogenesis is an essential biological process that plays a vital role in the tumorigenesis, diabetic retinopathy, and macular degeneration. NADPH oxidase 4 (Nox4), which was positively associated with ROS production and angiogenesis, was elevated during H/R. This effect could be reversed through suppression of the transcription activity of G9a with BIX or siRNA. The Nrf2/HO-1 pathway, upstream of Nox, was activated in both BIX-treated mice and G9a-inhibited HUVECs. Collectively, our results demonstrated that inhibition of G9a-alleviated corneal angiogenesis by inhibiting Nox4-dependent ROS production through the Nrf2/HO-1 signaling pathway. Our results demonstrated that inhibition of G9a-alleviated corneal angiogenesis by inhibiting Nox4-dependent ROS production through the Nrf2/HO-1 signaling pathway These findings indicate that G9a may be a valuable therapeutic target for CoNV
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