Division of Genetics, Department of Cell and Molecular Biology and Microbiology, Faculty of Biological Sciences and Technologies, University of Isfahan, 81746-73441, Isfahan, Iran.
Isfahan Neuroscience Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.
Sci Rep. 2021 Apr 8;11(1):7713. doi: 10.1038/s41598-021-87131-z.
Alterations in the regulatory mechanisms that control the process of myelination in the nervous system, may lead to the impaired myelination in the Multiple sclerosis. The Hippo pathway is an important mediator of myelination in the nervous system and might contribute to the pathophysiology of MS. This study examined via qPCR the RNA expression of YAP1, TAZ, and CRB3 as the key effectors of the Hippo pathway and also, VDR in the peripheral blood of 35 sporadic, 37 familial MS patients; and also 34 healthy first-degree relatives of the familial MS patients (HFR) and 40 healthy individuals without a family history of the disease (control). The results showed the increased expression of VDR in the sporadic group, as compared to other groups. There was also an increased expression of TAZ in the familial and HFR groups, as compared to the control group. The familial and sporadic patients displayed a significantly lower level of expression of YAP1 in comparison to the HFR group. The increased expression level in the sporadic patients and control group, as compared to the HFR group, was seen in CRB3. We also assessed different clinical parameters and MRI characteristics of the patients. Overall, these findings suggest that Hippo pathway effectors and also VDR gene may play a potential role in the pathophysiology of the sporadic and familial forms of MS. Confirmation of different gene expression patterns in sporadic and familial MS groups may have obvious implications for the personalization of therapies in the disease.
神经系统中髓鞘形成过程的调控机制发生改变，可能导致多发性硬化症中的髓鞘形成受损。Hippo 通路是神经系统中髓鞘形成的重要调节因子，可能有助于多发性硬化症的病理生理学。本研究通过 qPCR 检测了 Hippo 通路的关键效应因子 YAP1、TAZ 和 CRB3 以及外周血中的 VDR 在 35 例散发性、37 例家族性多发性硬化症患者中的 RNA 表达，以及 34 例家族性多发性硬化症患者的健康一级亲属（HFR）和 40 例无家族病史的健康个体（对照组）。结果显示，与其他组相比，散发性组 VDR 的表达增加。家族性和 HFR 组 TAZ 的表达也高于对照组。与 HFR 组相比，家族性和散发性患者的 YAP1 表达水平显著降低。与 HFR 组相比，散发性患者和对照组的 CRB3 表达水平升高。我们还评估了患者的不同临床参数和 MRI 特征。总体而言，这些发现表明 Hippo 通路效应因子和 VDR 基因可能在散发性和家族性多发性硬化症的病理生理学中发挥作用。在散发性和家族性多发性硬化症组中确认不同的基因表达模式可能对该疾病的个体化治疗具有明显的意义。
