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

ABSTRACT

BACKGROUND: Increased activity of the NF-κB signaling pathway boosts the progression of retinopathy in diabetic rats. OBJECTIVES: Using a bioinformatics website, we identified a site where miR-874 binds to the NF-κB p65. Therefore, we speculated that miR-874 might improve retinopathy in diabetic rats by inhibiting the NF-κB signaling pathway. MATERIAL AND METHODS: Ten healthy rats were taken as the control group. Sixty streptozotocin (STZ; 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 NC mimic), 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 injections were administered into the caudal vein. RESULTS: miR-874 could target the degradation of p65. Compared with the control group, model rats had reduced miR-874 expression, increased vascular endothelial growth factor (VEGF) and Ang2 protein expression, lowered end-diastolic velocity (EDV) and peak systolic velocity (PSV) of the central retinal artery (CRA) and blood velocity of central retinal vein (CRV) and CRA, heightened plasma viscosity (PV), blood viscosity (BV) and erythrocyte sedimentation rate (ESR) at all shear rates, decreased capillary pericytes (IPCs), increased vascular endothelial cells (VECs), and ascended p65 expression in the retina (all p < 0.05). Thus, it was shown that pathological changes appeared in the retina of diabetic rats. These indices improved in diabetic rats injected with the miR-874 mimic or EVP4593, but deteriorated in those injected with miR-874 inhibitor (all p < 0.05). EVP4593 also could alleviate the aggravation of retinopathy that was caused by miR-874 inhibition in diabetic rats. CONCLUSIONS: miR-874 modulates the NF-κB signaling pathway by targeting the degradation of p65 to further improve the retina of diabetic rats, thus demonstrating the beneficial effect of miR-874 on diabetic retinopathy in rats.