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miR-34a-5p 通过靶向 ENPP3 预测糖尿病神经病理性疼痛的风险并调节小胶质细胞中的神经炎症。

miR-34a-5p Predicts the Risk of Diabetic Neuropathic Pain and Mediates Neuroinflammation in Microglia via Targeting ENPP3.

机构信息

Department of Pain, Zibo Central Hospital, Zibo, China.

Department of Neurology, Zibo Central Hospital, Zibo, China.

出版信息

Immunol Invest. 2024 Nov;53(8):1348-1358. doi: 10.1080/08820139.2024.2400550. Epub 2024 Sep 9.

DOI:10.1080/08820139.2024.2400550
PMID:39252196
Abstract

INTRODUCTION

The pathogenesis of diabetic neuropathic pain (DNP) is complex involving various processes, which need exploring reliable biomarkers for its early detection and severity prediction.

METHODS

Study enrolled 181 patients diagnosed with diabetes, among which 74 patients developed DNP. Serum miR-34a-5p levels were compared between DNP patients and non-DNP patients by polymerase chain reaction (PCR), and the potential of miR-34a-5p in predicting the risk and discriminating patients with DNP was evaluated. The regulatory effect of miR-34a-5p on the inflammation, proliferation, and polarization of microglia was evaluated in HMC3 cells treated with high glucose.

RESULTS

Upregulated miR-34a-5p was identified as a risk factor and discriminated DNP patients miR-34a-5p was positively correlated with the levels of triglyceride ( = 0.797), fasting blood glucose ( = 0.840), and glycated hemoglobin ( = 0.894) of DNP patients. In HMC3 cells, the high-glucose-induced inflammation, promoted cell growth and caused polarization. The knockdown of miR-34a-5p showed the significant protective effect of microglia activation by high glucose, which was reversed by silencing ENPP3.

DISCUSSION

miR-34a-5p served as a biomarker for the prediction and early detection of DNP and mediated microglia inflammation caused by DNP via modulating ENPP3.

摘要

简介

糖尿病性神经病理性疼痛(DNP)的发病机制复杂,涉及多种过程,需要探索可靠的生物标志物来进行早期检测和严重程度预测。

方法

研究纳入了 181 名被诊断患有糖尿病的患者,其中 74 名患者发生了 DNP。通过聚合酶链反应(PCR)比较 DNP 患者和非 DNP 患者的血清 miR-34a-5p 水平,并评估 miR-34a-5p 预测风险和区分 DNP 患者的潜力。通过用高葡萄糖处理 HMC3 细胞来评估 miR-34a-5p 对小胶质细胞炎症、增殖和极化的调节作用。

结果

上调的 miR-34a-5p 被鉴定为风险因素,并区分了 DNP 患者 miR-34a-5p 与 DNP 患者的甘油三酯(r=0.797)、空腹血糖(r=0.840)和糖化血红蛋白(r=0.894)水平呈正相关。在 HMC3 细胞中,高葡萄糖诱导的炎症、促进细胞生长并导致极化。miR-34a-5p 的敲低显示出对高葡萄糖引起的小胶质细胞激活的显著保护作用,而沉默 ENPP3 则逆转了这种作用。

讨论

miR-34a-5p 可作为 DNP 预测和早期检测的生物标志物,并通过调节 ENPP3 介导 DNP 引起的小胶质细胞炎症。

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