MicroRNA-155 mimics ameliorates nerve conduction velocities and suppresses hyperglycemia-induced pro-inflammatory genes in diabetic peripheral neuropathic mice

摘要

Background: MicroRNA-155 (miR-155) regulates inflammatory cytokines, however its role in Diabetic neuropathy (DN) remains unexplored. Methods: A strain of mice (db/db) having type II diabetes were studied for expression of miR-155 in plasma and in sciatic nerves. The miR-155 mimic treated mice were studied for effect on motor and sensory nerve conduction velocities along with blood perfusion in sciatic nerves and response to thermal stimuli test. The mice were evaluated for density of blood vessels, quantity of intra-epidermal nerve fibers (IENF), diameters of axons & thickness of myelin sheath of sciatic nerves. Bioinformatics analysis was done to confirm target genes of miR-155. Results: The db/db mice showed significant suppression of miR-155 in sciatic nerves. The treatment of miR-155 mimic elevated levels of miR-155 in both sciatic nerves and plasma; it also enhanced the blood flow in sciatic nerves and velocities of conduction for both sensory and motor nerves. The treatment showed significant decrease in the threshold to thermal stimuli in db/db mice. A significant improvement in density of perfused blood vessels was observed, along with elevation of IENF and thickness of myelin and axon diameters of sciatic nerves. The treatment attenuated levels of TNF-α, iNOS, IL1-β and Ym1. Microarray analysis showed that the treatment decreased the expression of proinflammatory genes TRAF2 and Notch2, SORT1 and were identified as target by in silico studies. Conclusion: Treatment of miR-155 mimic in db/db mice attenuated DN, suppressed diabetic associated proinflammatory genes and confirmed miR-155 mimic as therapeutic strategy for treating DN.