The Impact of LncRNA Nuclear-Enriched Abundant Transcript 1-Mediated Regulation of ASK1 Expression via miR-20a on High Glucose-Induced Retinal Vascular Endothelial Cell Injury

Abstract

This study investigates how long non-coding RNA (LncRNA) NEAT1 influences high glucose-induced damage in human retinal vascular endothelial cells (hRECs). Different experimental groups were established, including normal, high glucose, LncRNA NEAT1 knockdown, and miR-20a inhibition. Assessments were conducted for molecular and functional changes. In high glucose conditions, NEAT1 expression increased while miR-20a expression decreased in hRECs. Silencing NEAT1 reduced its levels and increased miR-20a expression. Consequently, reactive oxygen species (ROS), MDA, 4-HNE, IL-1β, TNF-α, ICAM-1, ASK1, VEGF, and p-p38 MAPK/p38 MAPK ratio decreased. This led to diminished cell proliferation, migration, and tube formation in hRECs. The impact of NEAT1 silencing was partially reversed by miR-20a inhibition, suggesting NEAT1′s regulatory role via miR-20a. NEAT1 suppressed miR-20a and ASK1 protein levels. Additionally, LncRNA NEAT1 sequestered miR-20a, contributing to ASK1 downregulation. This process also suppressed p38 MAPK activation, further inhibiting hREC functions. In summary, NEAT1 modulated high glucose-induced hREC injury by downregulating miR-20a and subsequently impacting ASK1 and p38 MAPK pathways, thereby impairing cell functions. This study provides insights into potential therapeutic targets for diabetic retinopathy.