Stigmasterol Inhibits High Glucose Induced Proliferation and Angiogenesis of Retinal Endothelial Cells by Regulating Mitogen-Activated Protein Kinase Signaling Pathway

Abstract

Diabetic retinopathy, a microvascular complication, is characterized by angiogenesis of vascular cells in retina. High glucose has been shown to stimulate neovascularization and contribute to the retinal angiogenesis. Stigmasterol exerts antidiabetic effect through protection of β-cell function. However, its role in diabetic retinopathy has not been examined. While stigmasterol alone had no cytotoxic effects on human retinal endothelial cell, stigmasterol reduced the viability of high glucose-stimulated human retinal endothelial cells. Furthermore, the migration of human retinal endothelial cells stimulated by high glucose was repressed by stigmasterol. High glucose promoted formation of capillary-like structures in human retinal endothelial cells, whereas stigmasterol decreased the total branch points in high glucose-stimulated human retinal endothelial cells. Lastly, stigmasterol attenuated high glucose-stimulated increase in the expression of vascular endothelial growth factor and vascular endothelial growth factor receptor proteins in human retinal endothelial cells. Also, the enhanced phosphorylation of extracellular signal-regulated kinase 1/2, p38, a stress stimulated kinase, and c-Jun NH2-terminal kinase in human retinal endothelial cells stimulated by high glucose was restored by stigmasterol treatment. In conclusion, stigmasterol exerts antiproliferative and antiangiogenic effects against high glucose-stimulated human retinal endothelial cells through inactivation of mitogen-activated protein kinase signaling.