Department of Genetics, Faculty of Medicine, International Campus, Shahid Sadoughi University of Medical Sciences and Health Services, Yazd, Iran.
Department of Genetics, Faculty of Medicine, Shahid Sadoughi University of Medical Sciences and Health Services, Yazd, Iran.
J Cell Physiol. 2019 Nov;234(11):19842-19851. doi: 10.1002/jcp.28583. Epub 2019 Apr 10.
Considerable advances have been made in identification of the involvement of immune modulators in diseases. There is growing evidence on the role of complement pathway in pathogenesis and course of multiple sclerosis (MS). Moreover, it has been recognized that microRNAs (miRNAs) play an essential role in modulation and development of immune response in the central nervous system. We aimed to investigate the expression profile of complement factor H (CFH) and miR-146a genes in experimental autoimmune encephalomyelitis (EAE) mouse model of MS to detect the possible roles of CFH and miR-146a as biomarkers of MS disease stats. Expression of CFH and miR-146a genes in liver and brain tissues of EAE mice was measured in acute and chronic phases of disease compared to matched controls using real-time polymerase chain reaction. In the liver, increased expression of CFH gene was observed in the chronic phase compared to the acute phase. However, no significant difference was observed between acute and chronic phase mice with normal mice, while miR-146a expression was significantly decreased in livers of EAE mice in chronic group compared to acute and control groups. The expression of CFH gene in brain had a significant decrease in acute and chronic phases compared to healthy mice. Taken together, these observations indicate probable implication of complement system and miR-146a in course of immune-related diseases and reveal more facts about the pathogenesis of MS. However, further work is needed to determine protein levels of CFH and other possible targets of miR-146a in serum and cerebrospinal fluid of MS patients.
在鉴定免疫调节剂在疾病中的作用方面已经取得了相当大的进展。越来越多的证据表明补体途径在多发性硬化症（MS）的发病机制和病程中起作用。此外，人们已经认识到 microRNAs（miRNAs）在中枢神经系统免疫反应的调节和发展中起着至关重要的作用。我们旨在研究补体因子 H（CFH）和 miR-146a 基因在实验性自身免疫性脑脊髓炎（EAE）MS 小鼠模型中的表达谱，以检测 CFH 和 miR-146a 作为 MS 疾病状态生物标志物的可能作用。使用实时聚合酶链反应比较急性和慢性疾病阶段与匹配对照的 EAE 小鼠肝脏和脑组织中 CFH 和 miR-146a 基因的表达。在肝脏中，与急性阶段相比，慢性阶段 CFH 基因的表达增加。然而，与急性阶段相比，急性和慢性阶段的正常小鼠之间没有观察到显著差异，而慢性组 EAE 小鼠肝脏中 miR-146a 的表达与急性组和对照组相比明显降低。与健康小鼠相比，大脑中 CFH 基因的表达在急性和慢性阶段均显著降低。综上所述，这些观察结果表明补体系统和 miR-146a 可能参与免疫相关疾病的过程，并揭示了更多关于 MS 发病机制的事实。然而，需要进一步的工作来确定 MS 患者血清和脑脊液中 CFH 蛋白水平和其他可能的 miR-146a 靶标。
