Lactate-binding protein DNMT3A in HRMECs promotes angiogenesis by upregulating VEGFA through HIF-1α lactylation.

ABSTRACT:

Background

Ocular neovascularization is a leading cause of blindness. Hypoxia is associated with retinal angiogenesis. Hypoxia results in lactate accumulation, which typically precedes protein lactylation, and this plays a crucial role in ocular neovascularization. However, the underlying mechanism remains unclear. Here, we investigate the role of the DNA methyltransferase, DNMT3A, in regulating lactylation following hypoxia in ocular neovascularization.

Results

DNMT3A controls endothelial cell angiogenesis via regulating lactate-derived HIF-1α lactylation. During oxygen-induced retinopathy progression, we detected increased levels of DNMT3A, HIF-1α lactylation, and vascular endothelial growth factor (VEGF) in endothelial cells. Exogenous lactate administration significantly

SUBMITTER: Wang X 

PROVIDER: S-EPMC12577310 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature