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. 2017 Oct 4:10:2395-2403.
doi: 10.2147/JPR.S133755. eCollection 2017.

The role of miR-190a-5p contributes to diabetic neuropathic pain via targeting SLC17A6

Di Yang #  1 , Qinyan Yang #  1 , Xinchuan Wei  1 , Yang Liu  1 , Ding Ma  1 , Jiaceng Li  1 , Yongling Wan  1 , Yao Luo  1
Affiliations

The role of miR-190a-5p contributes to diabetic neuropathic pain via targeting SLC17A6

Di Yang et al. J Pain Res. .

Abstract

Introduction: MicroRNAs play a key role in neuropathic pain. In a previous study, miR-190a-5p was significantly downregulated in diabetic neuropathic pain (DNP). However, the role and pathological mechanism of miR-190a-5p in DNP still remain unclear.

Materials and methods: DNP model was established. The paw withdrawal thresholds were measured to assess the mechanical nociceptive response. Dual-luciferase reporter assay was used to confirm the target gene of microRNA. The expressions of microRNA, gene, and protein were detected by the quantitative real-time polymerase chain reaction or Western blot. The levels of IL-1β and IL-6 were detected with the enzyme-linked immuno sorbent assay.

Results: Compared with the control sample, the expression of miR-190a-5p was decreased and SLC17A6 was increased in the spinal tissue from those developing DNP. The bioinformatics and luciferase reporter assay demonstrated that SLC17A6 is a direct target of miR-190a-5p. Up-regulation of miR-190a-5p and inhibition of SLC17A6 could significantly weaken the painful behavior and reduce IL-1β and IL-6 level in DNP.

Conclusion: miR-190a-5p is involved in DNP via targeting SLC17A6, and miR-190a-5p and SLC17A6 may be the therapeutic targets of this disease.

Keywords: DNP; IL-1β and IL-6; SLC17A66; miR-190a-5p; painful behavior; spinal tissue.

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Conflict of interest statement

Disclosure The authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
The characteristic of diabetic mice induced by streptozocin (STZ) and mechanical allodynia. (A) Change in blood glucose level; (B) change in body weight; (C) change in paw withdrawal thresholds; (D) correlation between blood glucose level and paw withdrawal thresholds. Note: **p-value<0.01 was considered to represent a statistically significant difference. Abbreviation: w, week.
Figure 2
Figure 2
The expression of miR-190a-5p and SLC17A6 in lumbar spinal dorsal horn from diabetic mice. (A) The expression of miR-190a-5p; (B) the gene expression of SLC17A6; (C) the protein expression of SLC17A6. Note: **p-value<0.01 was considered to represent a statistically significant difference. Abbreviation: w, week.
Figure 3
Figure 3
The dual-luciferase reporter assay of miR-190a-5p. (A) Putative mmu-miR-190a-5p-binding sequence in the SLC17A6 3′-UTR and the site-directed mutant SLC17A6 3′-UTR. (B, C) The WT or Mut reporter plasmids or NC or miR-190a-5p mimics were co-transfected into HEK293T cells. Note: **p-value<0.01 was considered to represent a statistically significant difference. Abbreviations: Mut, mutated; NC, normal control; WT, wild-type.
Figure 4
Figure 4
The therapeutic effect of miR-190a-5p in diabetic neuropathic pain. (A) The expression of miR-190a-5p; (B) the gene expression of SLC17A6; (C) the protein expression of SLC17A6; (D, E) the level of IL-1β and IL-6; (F) change in paw withdrawal thresholds. Note: **p-value<0.01 was considered to represent a statistically significant difference. Abbreviations: Before, before injection with lentiviral vectors; After, at the fourth week after injection with lentiviral vectors.
Figure 5
Figure 5
The therapeutic effect of SLC17A6 inhibitor in diabetic neuropathic pain. (A) The protein expression of SLC17A6; (B, C) the level of IL-1β and IL-6; (D) change in paw withdrawal thresholds. Note: **p-value<0.01 was considered to represent a statistically significant difference. Abbreviations: Before, before injection with SLC17A6 inhibitor; After, at first week after injection with SLC17A6 inhibitor.
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References

    1. Gu Y, Dennis SM. Are falls prevention programs effective at reducing the risk factors for falls in people with type-2 diabetes mellitus and peripheral neuropathy: a systematic review with narrative synthesis. J Diabetes Complications. 2017;31(2):504–516. - PubMed
    1. Shenoy AM. Guidelines in practice: treatment of painful diabetic neuropathy. Continuum (Minneap Minn) 2012;18(1):192–198. - PubMed
    1. Feldman EL, Nave KA, Jensen TS, Bennett DL. New horizons in diabetic neuropathy: mechanisms, bioenergetics, and pain. Neuron. 2017;93(6):1296–1313. - PMC - PubMed
    1. Nickerson DS. Rationale, science, and economics of surgical nerve decompression for diabetic neuropathy foot complications. Clin Podiatr Med Surg. 2016;33(2):267–282. - PubMed
    1. Stolf AM, Cardoso CC, Acco A. Effects of silymarin on diabetes mellitus complications: a review. Phytother Res. 2017;31(3):366–374. - PubMed

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