Department of Molecular Biology Genetics, İstanbul Medeniyet University, İstanbul, Turkey.
Department of Neuroscience, Aziz Sancar Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey.
Genet Test Mol Biomarkers. 2021 Nov;25(11):720-726. doi: 10.1089/gtmb.2021.0183.
Brain-derived neurotrophic factor (BDNF) levels are reduced in advanced stages of multiple sclerosis (MS) and may be associated with reduced regenerative capability in progressive MS. This has brought increased attention to factors regulating BDNF production in MS. Our aim was to investigate the link between neurotrophin-regulating microRNAs (miRNA) and disease progression in MS. Serum levels of BDNF and peripheral blood mononuclear cell (PBMC) expression levels of miR-132-3p, miR-106b-5p and miR-19b-3p were respectively measured by ELISA and real time PCR in twelve relapsing remitting MS (RRMS) patients, seven secondary progressive MS (SPMS) patients and fourteen healthy controls. Serum BDNF levels were significantly reduced in SPMS patients, while selected miRNAs were significantly upregulated in PBMC of RRMS and SPMS patients. miR-106b-5p and miR-19b-3p respectively showed the highest sensitivity and specificity for MS diagnosis by receiver operating characteristic curve analysis. There was a negative correlation between levels of BDNF and the miRNAs in RRMS. Likewise, levels of BDNF and the investigated miRNAs showed positive and negative correlations respectively with the expanded disability status scale in RRMS and SPMS patients. miR-132-3p and miR-106b-5p levels showed positive correlations with the progression index in SPMS patients. Our results suggest that increased disability is associated with downregulation of miR-132-3p, miR-106b-5p and miR-19b-3p in RRMS patients and putatively promotes increased production of neuroprotective BDNF as a compensatory mechanism. This link between the investigated miRNAs and BDNF in RRMS does not appears to hold for SPMS. This might be one of the factors contributing to reduced regenerative ability in the progressive stage of MS.
脑源性神经营养因子（BDNF）水平在多发性硬化症（MS）的晚期降低，并且可能与进行性 MS 中的再生能力降低有关。这引起了人们对调节 MS 中 BDNF 产生的因素的更多关注。我们的目的是研究神经营养因子调节 microRNA（miRNA）与 MS 疾病进展之间的联系。通过 ELISA 和实时 PCR 分别测量了 12 名复发缓解型多发性硬化症（RRMS）患者、7 名继发进展型多发性硬化症（SPMS）患者和 14 名健康对照者的血清 BDNF 水平和外周血单个核细胞（PBMC）中 miR-132-3p、miR-106b-5p 和 miR-19b-3p 的表达水平。SPMS 患者的血清 BDNF 水平显著降低，而 RRMS 和 SPMS 患者的 PBMC 中选定的 miRNA 则显著上调。通过接收者操作特征曲线分析，miR-106b-5p 和 miR-19b-3p 分别对 MS 诊断具有最高的敏感性和特异性。RRMS 患者的 BDNF 水平与 miRNA 呈负相关。同样，RRMS 和 SPMS 患者的 BDNF 水平和研究的 miRNA 分别与扩展残疾状况量表呈正相关和负相关。SPMS 患者的 miR-132-3p 和 miR-106b-5p 水平与进展指数呈正相关。我们的结果表明，RRMS 患者的残疾程度增加与 miR-132-3p、miR-106b-5p 和 miR-19b-3p 的下调有关，推测这可能促进了神经保护 BDNF 的产生，作为一种代偿机制。RRMS 中这些 miRNA 与 BDNF 之间的这种联系似乎不适用于 SPMS。这可能是 MS 进行性阶段再生能力降低的因素之一。
