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Repository of Research and Investigative Information

Hormozgan University of Medical Sciences

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

(2015) Deregulation of NF-kappa B-miR-146a negative feedback loop may be involved in the pathogenesis of diabetic neuropathy. JOURNAL OF PHYSIOLOGY AND BIOCHEMISTRY.

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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-kappa B) was measured in the sciatic nerve of rats using the real time-PCR method. Moreover, the activity of NF-kappa 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-kappa B, and a twofold decrease in the expression of TRAF6 were observed in the sciatic nerve of diabetic rats. Furthermore, the NF-kappa B activity and the concentration of TNF-alpha, interleukin 6 (IL-6), and interleukin 1 beta (IL-1 beta) in the sciatic nerve of diabetic rats were higher than in those of control counterparts. These results suggest that a defect in the NF-(DB)-B-0-miR-146a negative feedback loop may be involved in the pathogenesis of diabetic neuropathy.

Item Type: Article
Keywords: Diabetes; Sciatic nerve; MicroRNA-146a; NF-kappa B; IRAK1; TRAF6 NF-KAPPA-B; BETA-CELL DYSFUNCTION; OXIDATIVE STRESS; PROINFLAMMATORY CYTOKINES; RATS; RESVERATROL; COMPLICATIONS; MECHANISMS; MICRORNAS; HYPERGLYCEMIA
Subjects: QU Biochemistry. Cell Biology and Genetics > QU 300-560 Cell Biology and Genetics
endocrine
Depositing User: مهندس هدی فهیم پور
URI: http://eprints.hums.ac.ir/id/eprint/5337

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