• Xian Shuang Liu, Baoyan Fan, Alexandra Szalad, Longfei Jia, Lei Wang, Xinli Wang, Wanlong Pan, Li Zhang, Ruilan Zhang, Jiani Hu, Xiao Ming Zhang, Michael Chopp, and Zheng Gang Zhang.
• Department of Neurology, Henry Ford Health System, Detroit, MI xsliu@neuro.hfh.edu.
• Diabetes. 2017 Dec 1; 66 (12): 3111-3121.

AbstractMicroRNA-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 2 diabetes exhibited substantial downregulation 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 fluorescein isothiocyanate-dextran-perfused blood vessels and increased the number of intraepidermal nerve fibers, myelin thickness, and axonal diameters of sciatic nerves. In addition, miR-146a treatment reduced and increased classically and alternatively activated 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.© 2017 by the American Diabetes Association.

25 keywords...

hide…