Deregulation of NF-?B-miR-146a negative feedback loop may be involved in the pathogenesis of diabetic neuropathy

Abstract

The current study was designed to explore whether microRNA-146a and its adapter proteins (tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6) and interleukin-1 receptor-associated kinase 1 (IRAK1)) are involved in the pathogenesis of diabetes neuropathy. Twelve male Sprague Dawley rats were randomized into control and diabetic groups (n = 6). Diabetes was induced by a single-dose injection of nicotinamide (110آ mg/kg; i.p.), 15آ min before injection of streptozotocin (50آ mg/kg; i.p.) in 12-h-fasted rats. Diabetic neuropathy was evaluated by hot plate and tail emersion tests, 2آ months after the injection of streptozotocin. The gene expression level of microRNA-146a (miR-146a), IRAK1, TRAF6, and nuclear factor kappa B (NF-?B) was measured in the sciatic nerve of rats using the real time-PCR method. Moreover, the activity of NF-?B and the concentration of pro-inflammatory cytokines were determined by the ELISA method. In comparison with the control group, a threefold increase in the expression of miR-146a and NF-?B, and a twofold decrease in the expression of TRAF6 were observed in the sciatic nerve of diabetic rats. Furthermore, the NF-?B activity and the concentration of TNF-?, interleukin 6 (IL-6), and interleukin 1? (IL-1?) in the sciatic nerve of diabetic rats were higher than in those of control counterparts. These results suggest that a defect in the NF-?B-miR-146a negative feedback loop may be involved in the pathogenesis of diabetic neuropathy. é 2015, University of Navarra.