Involvement of the miR‐128‐3p/KDM3A/NLRP3 Axis in High Glucose‐Induced Inflammatory Injury in Retinal Endothelial Cells

This study explores the regulatory mechanism of the miR‐128‐3p in diabetic retinopathy (DR)‐associated inflammatory injury. A cellular model of DR was established by inducing immortalized human retinal endothelial cells (IM‐HRECs) with high‐glucose (HG). Cell viability was evaluated by CCK‐8 assay, and the levels of TNF‐α, IL‐1β, and IL‐10 were measured by ELISA. RT‐qPCR was performed to determine miR‐128‐3p expression, and miR‐128‐3p mimics were transfected into cells to verify its regulatory role in DR‐associated inflammatory injury. miR‐128‐3p was predicted by Starbase to bind to the 3′ UTR of KDM3A, which was verified by dual‐luciferase assay. The expressions of KDM3A and NLRP3 in cells were examined by Western blotting, and the enrichment of KDM3A and H3K9me2 on the NLRP3 promoter was measured by Ch‐IP assay. The results revealed that HG treatment significantly reduced both IM‐HREC viability and IL‐10 levels, increased the levels of TNF‐α and IL‐1β, and downregulated the expression of miR‐128‐3p. Overexpression of miR‐128‐3p reduced inflammation in IM‐HRECs induced by HG. The proposed mechanism involves targeting of the KDM3A 3′ UTR by miR‐128‐3p, leading to reduced KDM3A expression, while KDM3A increased NLRP3 expression by reducing H3K9me2. In conclusion, upregulation of miR‐128‐3p increases the histone H3K9me2 level by inhibiting KDM3A expression, thereby reducing NLRP3 expression and suppressing DR inflammatory injury.