The role of miR-146a in dorsal root ganglia neurons of experimental diabetic peripheral neuropathy

Abstract

Sensory neurons mediate diabetic peripheral neuropathy. Using a mouse model of diabetic peripheral neuropathy (db/db mice) and cultured dorsal root ganglion (DRG) neurons, the present study showed that hyperglycemia downregulated miR-146a expression and elevated interleukin-1 receptor activated kinase (IRAK1) and tumor necrosis factor receptor-associated factor 6 (TRAF6) levels in DRG neurons. In vitro, elevation of miR-146a by miR-146a mimics in DRG neurons increased neuronal survival under high glucose conditions. Downregulation and elevation of miR-146a in DRG neurons, respectively, were inversely related to IRAK1 and TRAF6 levels. Treatment of diabetic peripheral neuropathy with sildenafil, a phosphodiesterase type 5 inhibitor, augmented miR-146a expression and decreased levels of IRAK1 and TRAF6 in the DRG neurons. In vitro, blockage of miR-146a in DRG neurons abolished the effect of sildenafil on DRG neuron protection and downregulation of IRAK1 and TRAF6 proteins under hyperglycemia. Our data provide the first evidence showing that miR-146a plays an important role in mediating DRG neuron apoptosis under hyperglycemic conditions.

MicroRNA-146a-5p attenuates neuropathic pain via suppressing TRAF6 signaling in the spinal cord

“…Additionally, miR-146a expression in the sensory neuron of DRG was much lower in 24-week-old diabetic db/db mice than that in non-diabetic mice (Wang et al, 2014). However, we found that Fig.…”

“…It was noteworthy that (1) although SNL increased miR-146a-5p levels at 10 and 21 days, these levels were not sufficient to significantly reduce the expression of the TRAF6, and overexpression miR-146a-5p is required to exert an analgesic effect; (2) intrathecal drug delivery can affect both spinal cord and DRG (Butler et al, 2005;Zhuang et al, 2006). Intrathecal miR-146a-5p mimic may also exert anti-nociceptive effect via regulating the function of TRAF6 and IRAK1 in the DRG (Wang et al, 2014).…”

Noncoding RNAs and Their Potential Therapeutic Applications in Tissue Engineering

“…Neural stem/progenitor cells Promote proliferation miR-25 [12]; miR-137 [13]; miR-184 [14]; miR-195 [15] Induce differentiation miR-9, siRNA-TLX [16]; let-7d [17]; miR-137 [13]; miR-184 [14]; miR-195 [15]; miR-34a [18]; lncRNA-BDNF-AS, siRNA-BDNF-AS [19] Mesenchymal stem cells Induce differentiation miR-9 [20]; miR-124 [21] Reduce differentiation miR-128 [22] Neuronal cells Inhibit cell death miR-223 [23]; miR-181c [24]; miR-592 [25]; miR-424 [26]; miR-23a-3p [27]; miR-23a/b, miR-27a/b, siRNA-Apaf-1 [28] Promote cell death miR-134 [29]; miR-200c [30]; miR-30a/b [31][32][33]; miR-124 [34]; miR-711 [35] Regulate degeneration and apoptosis miR-20a [36]; miR-29b [37]; miR-146a, siRNA-miR146a [38] Promote neurite outgrowth miR-7 [39]; miR-21 [40]; miR-222, siRNA-PTEN [41]; miR-8 [42]; miR-431 [43]; miR-145 [44]; lncRNA-uc.217 [45]; miR-138, siRNA-SIRT1 [46] Microglial cells Inhibit inflammation let-7c [47]; miR-124, siRNA-C/EBP-α [48] Promote pro-inflammation miR-155 [49] Inhibit activation let-7c-5p [50] Astrocytes P...…”

“…Following peripheral nerve injury, overexpression of miR-21 and miR-222 reduces apoptosis and enhances the viability of cultured dorsal root ganglion (DRG) neurons [40,41]. miR-146a mediates apoptosis in DRG neurons under hyperglycemic conditions [38].…”

Circulating microRNAs and diabetes: potential applications in medical practice

“…As intracellular miRNAs appear to be deregulated in this diabetic complication, it would be worthwhile to investigate whether circulating miRNAs could be potential biomarkers of this disease [68,69].…”