Department of Endocrinology, The First Affiliated Hospital of Soochow University, Suzhou City, Jiangsu Province, 215000, China.
Department of Endocrinology, Shanghai International Medical Center, Shanghai, 200318, China.
Acta Biochim Pol. 2020 Dec 17;67(4):587-593. doi: 10.18388/abp.2020_5451.
MicroRNAs play a crucial role in diabetic peripheral neuropathic pain (DPNP). miR-590-3p is a novel miRNA and involved in multiple diseases. However, the pathological mechanism of miR-590-3p in DPNP needs to be elucidated.
The db/db mice and db/m mice were selected to mimic diabetes and control, respectively, for in vivo studies. The miR-590-3p agomir was injected into db/db mice and pain-related behavioral tests were performed. The interaction of miR-590-3p with target gene was confirmed by dual-luciferase reporter assay. The expression of target gene was determined by qRT-PCR and western blot assay. The levels of inflammatory cytokines were measured by enzyme-linked immunosorbent assay (ELISA).
miR-590-3p was down-regulated in diabetic peripheral neuropathy mice. More importantly, miR-590-3p agomir alleviated pain-related behavior, reduced TNF-α, IL-1β and IL-6 concentrations, and inhibited neural infiltration by immune cells in db/db mice. Interestingly, RAP1A was predicted to be the target of miR-590-3p by Targetscan, and was actually regulated by miR-590-3p. Finally, the rescue experiments proved that overexpression of RAP1A partially abrogated the suppressive impact of miR-590-3p on T cells proliferation and migration.
miR-590-3p ameliorates DPNP via targeting RAP1A and inhibiting T cells infiltration, indicating that exogenous miR-590-3p may be a potential candidate for clinical treatment of DPNP.
MicroRNAs 在糖尿病周围神经性疼痛（DPNP）中发挥着关键作用。miR-590-3p 是一种新的 miRNA，涉及多种疾病。然而，miR-590-3p 在 DPNP 中的病理机制仍需阐明。
选择 db/db 小鼠和 db/m 小鼠分别模拟糖尿病和对照，进行体内研究。将 miR-590-3p agomir 注射到 db/db 小鼠中，并进行疼痛相关行为测试。通过双荧光素酶报告基因检测证实 miR-590-3p 与靶基因的相互作用。通过 qRT-PCR 和 Western blot 检测靶基因的表达。通过酶联免疫吸附试验（ELISA）测量炎症细胞因子的水平。
miR-590-3p 在糖尿病周围神经病变小鼠中表达下调。更重要的是，miR-590-3p agomir 缓解了疼痛相关行为，降低了 TNF-α、IL-1β 和 IL-6 的浓度，并抑制了 db/db 小鼠中免疫细胞的神经浸润。有趣的是，Targetscan 预测 RAP1A 是 miR-590-3p 的靶基因，并且实际上受到 miR-590-3p 的调控。最后，挽救实验证明，RAP1A 的过表达部分消除了 miR-590-3p 对 T 细胞增殖和迁移的抑制作用。
miR-590-3p 通过靶向 RAP1A 抑制 T 细胞浸润来改善 DPNP，表明外源性 miR-590-3p 可能是治疗 DPNP 的潜在候选药物。
