Procyanidin C1 modulates microglia cellular iron homeostasis via targeting HuR/ACSL4 pathway and alleviates high-glucose-induced ferroptosis in diabetic retinopathy.
TL;DR
Investigating the potential role of the RNA-binding protein human antigen R (HuR) in mediating ferroptosis during DR progression, as well as the protective effects of Procyanidin C1 (PC1), demonstrated that PC1 significantly alleviated oxidative stress and ferroptosis in both diabetic mice and high-glucose-treated BV2s.
Abstract
Diabetic retinopathy (DR), one of the most prevalent microvascular complications of diabetes, is a vision-threatening ocular disease. Although ferroptosis has been implicated in DR development, research on its underlying mechanisms and targeted therapeutics remains limited. Procyanidins, a class of polyphenolic compounds, exhibit robust anti-inflammatory properties and regulatory effects on various pathological processes. Herein, we investigated the potential role of the RNA-binding protein human antigen R (HuR) in mediating ferroptosis during DR progression, as well as the protective effects of Procyanidin C1 (PC1). Streptozotocin-induced diabetic mice and high-glucose-exposed BV2 microglial cells (BV2s) were treated with PC1 to evaluate oxidative stress and the expression of ferroptosis markers. The interaction between HuR and ACSL4 was characterized using ribonucleoprotein (RNP) immunoprecipitation (IP) and mRNA stability assays. Our results demonstrated that PC1 significantly alleviated oxidative stress and ferroptosis in both diabetic mice and high-glucose-treated BV2s. Mechanistically, post-transcriptional regulation by HuR via stabilizing Acsl4 mRNA contributes to the acceleration of ferroptosis during DR progression. Ultimately, PC1 suppresses DR advancement by targeting the HuR-ACSL4 signaling axis, highlighting its potential as a therapeutic intervention.