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

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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-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.

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Acknowledgments

The grant of this study was supported by Neurosciences Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

Conflict of interest

The authors have declared that there is no conflict of interest.

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Authors and Affiliations

  1. Neurosciences Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

    Nasibeh Yousefzadeh & Mohammad Reza Alipour

  2. Molecular Medicine Research Center, Hormozgan University of Medical Sciences, Bandar Abbas, Iran

    Farhad Ghadiri Soufi

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  1. Nasibeh Yousefzadeh
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  2. Mohammad Reza Alipour
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  3. Farhad Ghadiri Soufi
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Correspondence to Farhad Ghadiri Soufi.

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Yousefzadeh, N., Alipour, M.R. & Ghadiri Soufi, F. Deregulation of NF-кB–miR-146a negative feedback loop may be involved in the pathogenesis of diabetic neuropathy. J Physiol Biochem 71, 51–58 (2015). https://doi.org/10.1007/s13105-014-0378-4

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  • DOI: https://doi.org/10.1007/s13105-014-0378-4

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