title: Deregulation of NF-кB-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 (110 mg/kg; i.p.), 15 min before injection of streptozotocin (50 mg/kg; i.p.) in 12-h-fasted rats. Diabetic neuropathy was evaluated by hot plate and tail emersion tests, 2 months after the injection of streptozotocin. The gene expression level of microRNA-146a (miR-146a), IRAK1, TRAF6, and nuclear factor kappa B (NF-κB) was measured in the sciatic nerve of rats using the real time-PCR method. Moreover, the activity of NF-κB 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-κB, and a twofold decrease in the expression of TRAF6 were observed in the sciatic nerve of diabetic rats. Furthermore, the NF-κB activity and the concentration of TNF-α, interleukin 6 (IL-6), and interleukin 1β (IL-1β) in the sciatic nerve of diabetic rats were higher than in those of control counterparts. These results suggest that a defect in the NF-кB-miR-146a negative feedback loop may be involved in the pathogenesis of diabetic neuropathy.
authors.affiliation: Neurosciences Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Nasibeh
authors.initials: N
authors.lastname: Yousefzadeh
authors.forename: Mohammad Reza
authors.initials: MR
authors.lastname: Alipour
authors.forename: Farhad Ghadiri
authors.initials: FG
authors.lastname: Soufi
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D016022:Case-Control Studies; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced; D003929:Diabetic Neuropathies / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D005951:Glucose Tolerance Test; D018836:Inflammation Mediators / Q000378:metabolism; D007328:Insulin / Q000097:blood; D053592:Interleukin-1 Receptor-Associated Kinases / Q000235:genetics; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000378:metabolism; D048029:TNF Receptor-Associated Factor 6 / Q000235:genetics
chemical_list: D001786:Blood Glucose; D018836:Inflammation Mediators; D007328:Insulin; C554180:MIRN146 microRNA, rat; D035683:MicroRNAs; D016328:NF-kappa B; D012333:RNA, Messenger; D048029:TNF Receptor-Associated Factor 6; C547807:IRAK1 protein, rat; D053592:Interleukin-1 Receptor-Associated Kinases