miR-874 ameliorates retinopathy in diabetic rats by NF-κB signaling pathway

Abstract

Background: miRNAs participate in the development and progression of diabetic retinopathy (DR) and are involved in multiple pathogenesis of DR. High expression of NF-κB signaling pathway boosts the progression of retinopathy in diabetes rats. We found a site where miR-874 bound to the NF-κB p65 by the prediction on a bioinformatics website. Therefore, it was speculated that miR-874 might improve retinopathy in diabetic rats by inhibiting the NF-κB signaling pathway.Methods: Ten healthy Sprague-Dawley rats were taken as the control group. Sixty streptozotocin (60 mg/kg)-induced diabetes model rats were randomly divided into the model group (injection of normal saline), negative control (NC) agomir group (injection of overexpressed NC vector), miR-874 agomir group (injection of miR-874 mimic), miR-874 anti-agomir group (injection of miR-874 inhibitor), EVP4593 group (injection of NF-κB signaling pathway antagonist EVP4593), and miR-874 anti-agomir + EVP4593 group (injection of miR-874 inhibitor and EVP4593). All injection was via caudal vein.Results: miR-874 could target the degradation of p65. Compared with the control group, there were significantly reduced miR-874 expression, increased VEGF and Ang2 protein expressions, lowered end-diastolic velocity and peak systolic velocity of central retinal artery (CRA) and blood velocity of central retinal vein and CRA, heightened plasma viscosity, blood viscosity and erythrocyte sedimentation rate at all shear rates, decreased capillary pericytes, increased vascular endothelial cells, and ascended p65 expression in the retina of rats in the model group (all P < 0.05). It showed that pathological changes appeared in the retina of diabetes rats. These indexes showed the same results after miR-874 was inhibited (all P < 0.05). However, these indexes showed the opposite results in the miR-874 agomir group and EVP4593 group compared with the model group (all P < 0.05). EVP4593 could alleviate the aggravation of retinopathy that was caused by the inhibition of miR-874 in diabetes rats.Conclusions: miR-874 mediates the NF-κB signaling pathway by targeting the degradation of p65 to further improve the retina of diabetes rats, showing the improvement effect of miR-874 on diabetic retinopathy in rats.