黑色素瘤分化相关基因5在临床疾病中的研究进展

Research progress of MDA5 in clinical diseases

黑色素瘤分化相关基因5(Melanoma differentiation related gene 5,MDA5)是先天性免疫受体中RIG-Ⅰ样受体的成员之一,识别细胞质内的双链RNA,通过胞内信号传导诱导Ⅰ型干扰素的产生。它参与多种疾病过程,如病毒感染、真菌感染、自身免疫病和癌症。病毒感染时,MDA5可通过识别病毒RNA启动IRF3/7信号途径引起Ⅰ型IFN表达升高和NF-κB信号通路激活,抵抗病毒感染。也有研究指出,MDA5参与曲霉菌、白色念珠菌等真菌感染的免疫过程,但作用机制不清,可能与免疫紊乱有关。多种自身免疫病如Aicardi-Gtières综合征、皮肌炎、系统性红斑狼疮、1型糖尿病、白癜风是由MDA5的功能获得性突变,引发免疫紊乱所致。此外,MDA5能抵抗多种癌症细胞的增殖、诱导多种癌细胞凋亡。本文综述了MDA5在相关临床疾病中的作用及可能机制的研究进展。

Melanoma differentiation related gene 5(MDA5) is a member of RIG-Ⅰlike receptor among innate immune receptors. It recognizes double stranded RNA in cytoplasm and induces type Ⅰ interferon through intracellular signal transduction. It is involved in a variety of disease processes,such as viral infection,fungal infection,autoimmune diseases,and cancer. MDA5 can recognize viral RNA and activate IRF3/7 signaling pathway to increase type I IFN expression and NF-κB signaling pathway to resist viral infection. Some studies have also indicated that MDA5 is involved in the immune process of fungal infections such as aspergillus and candida albicans,but the mechanisms are still unclear and may be related to immune disorders. A variety of autoimmune diseases,such as Aicardi-Gtières syndrome,dermatomyositis,systemic lupus erythematosus,type 1 diabetes,and vitiligo,are caused by immune disorders caused by functional acquired mutations of MDA5. In addition,MDA5 can resist proliferation and induce apoptosis of various cancer cells. In this paper,the role of MDA5 in related clinical diseases and its possible mechanism are reviewed.