Recombinant human maspin inhibits high glucose-induced oxidative stress and angiogenesis of human retinal microvascular endothelial cells via PI3K/AKT pathway.

Abstract

Maspin is known as a tumor suppressor and a potent angiogenesis inhibitor, however, its effects on proliferative diabetic retinopathy (PDR) have not been fully elucidated. This study aimed at evaluating the effects of maspin on high glucose-induced oxidative stress and angiogenesis in human retinal microvascular endothelial cells (HRMECs). Herein, HRMECs were treated with 0.25, 0.5, or 1µM recombinant human maspin in the presence of 30mM glucose, and their proliferation, tube formation, and oxidative stress responses were further detected. Our results revealed that maspin inhibited the high glucose-induced proliferation, migration, and tube formation of HRMECs. Maspin also decreased reactive oxygen species, nitric oxide level, and increased glutathione S-transferase activity in HRMECs. Meanwhile, maspin reduced the mRNA and protein levels of hypoxia-inducible factor-1α and vascular endothelial growth factor in high glucose-stimulated cells in a dose-dependent manner. Additionally, the high glucose-induced elevation of phosphorylated phosphoinositide-3-kinase (p-PI3K) and phosphorylated AKT was also suppressed by maspin. In summary, our data suggest that maspin inhibits high glucose-induced proliferation, oxidative stress, and angiogenesis of HRMECs at least by modulating the PI3K/AKT pathway. Maspin may be a potential therapeutic agent for the prevention and treatment of PDR.