Abstract
Increased activity of the NF-κB signaling pathway boosts the progression of retinopathy in diabetic rats. 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. 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. 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. 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.
Highlights
This study aimed to explore the improvement effect of miR-874 on retinopathy in diabetic rats by NF-κB signaling pathway
Several studies have showed that the activity of NF-κB signaling pathway is significantly increased in diabetes rats, and the up-regulation of NF-κB p65 expression augments the generation of reactive oxygen species and further leads to the occurrence of microaneurysms, retinal neovascularization and vitreous hemorrhage, boosting the progression of retinopathy in diabetes rats [9,10,11]
Blood glucose level was increased in model group and normal in control group at about 4 mmol/l; the soaring of modeled rats’ blood glucose was slowed down in miR–874 agomir group and EVP4593 group; the soaring of modeled rats’ blood glucose was facilitated in miR–874 antiagomir group; EVP4593 neutralized the promotion of miR–847 anti-agomir on modeled rats’ blood glucose in miR–874 anti-agomir + EVP4593 group (Fig. 2A)
Summary
This study aimed to explore the improvement effect of miR-874 on retinopathy in diabetic rats by NF-κB signaling pathway. Diabetic retinopathy (DR) is a kind of microvascular complication, and it is triggered by the leakage of retinal capillary wall that is caused by the hyperglycemia of diabetic patients. Previous studies suggested that a series of pathophysiological changes had happened on the retina under the stimulation of persistent hyperglycemia, resulting in retinopathy [4,5,6,7,8]. Several studies have showed that the activity of NF-κB signaling pathway is significantly increased in diabetes rats, and the up-regulation of NF-κB p65 expression augments the generation of reactive oxygen species and further leads to the occurrence of microaneurysms, retinal neovascularization and vitreous hemorrhage, boosting the progression of retinopathy in diabetes rats [9,10,11]. MicroRNA (miRNA) is a non-coding single-stranded RNA molecule
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