5 years ago

MicroRNA-146a Mimics Reduce the Peripheral Neuropathy in Type II Diabetic Mice.

MicroRNA-146a (miR-146a) regulates multiple immune diseases. However, the role of miR-146a in diabetic peripheral neuropathy (DPN) has not been investigated. We found that mice (db/db) with type II diabetes exhibited substantial down-regulation of miR-146a in sciatic nerve tissue. Systemic administration of miR-146a mimics to diabetic mice elevated miR-146a levels in plasma and sciatic nerve tissue and substantially increased motor and sensory nerve conduction velocities by 29% and 11%, respectively, and regional blood flow by 50% in sciatic nerve tissue. Treatment with miR-146a mimics also considerably decreased the response in db/db mice to thermal stimuli thresholds. Histopathological analysis showed that miR-146a mimics markedly augmented the density of FITC-dextran perfused blood vessels and increased the number of intraepidermal nerve fibers (IENF), myelin thickness and axonal diameters of sciatic nerves. In addition, miR-146a treatment reduced and increased M1 and M2 macrophage phenotype markers, respectively. Analysis of miRNA target array revealed that miR-146a mimics greatly suppressed expression of many proinflammatory genes and downstream related cytokines. Collectively, our data indicate that treatment of diabetic mice with miR-146a mimics robustly reduces DPN and that suppression of hyperglycemia-induced proinflammatory genes by miR-146a mimics may underlie its therapeutic effect.

Publisher URL: http://doi.org/10.2337/db16-1182

DOI: 10.2337/db16-1182

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