MiR-125a-5p Regulates Vitamin D Receptor Expression in a Mouse Model of Experimental Autoimmune Encephalomyelitis

作     者：Han-Chun Long Rui Wu Chun-Feng Liu Fei-Long Xiong Zu Xu Dian He Yi-Fan Zhang Bing Shao Ping-An Zhang Guang-Yin Xu Lan Chu Han-Chun Long;Rui Wu;Chun-Feng Liu;Fei-Long Xiong;Zu Xu;Dian He;Yi-Fan Zhang;Bing Shao;Ping-An Zhang;Guang-Yin Xu;Lan Chu

作者机构：Department of NeurologyThe Affiliated Hospital of Guizhou Medical UniversityGuiyang 550001China Department of NeurologyThe Second Affiliated Hospital of Soochow UniversitySuzhou 215008China Institute of NeuroscienceSoochow UniversitySuzhou 215123China Department of NeurologyThe Affiliated Xingyi City Hospital of Guizhou Medical UniversityXingyi 562400China 

出 版 物：《Neuroscience Bulletin》 (神经科学通报（英文版）)

年 卷 期：2020年第36卷第2期

页      面：110-120页

核心收录：

学科分类：0710[理学-生物学] 1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 100204[医学-神经病学] 10[医学] 

基　　金：supported by the International Science and Technology Cooperation Plan of Guizhou Province,China[(2013)7027] the National Natural Science Foundation of China(81471137 and 31730040). 

主　　题：Multiple sclerosis Experimental autoimmune encephalomyelitis Vitamin D receptor MiR-125a-5p Myelin oligodendrocyte glycoprotein 35-55 peptides 

摘      要：Multiple sclerosis(MS)is a chronic and incurable autoimmune neurodegenerative disease of the central nervous system.Although the symptoms of MS can be managed by vitamin D3 treatment alone,this condition cannot be completely eradicated.Thus,there might be unknown factors capable of regulating the vitamin D receptor(VDR).Genome-wide analysis showed that miRNAs were associated with VDRs.We sought to determine the role and mechanism of action of miRNA-125a-5p and VDRs in a model of MS,mice with experimental autoimmune encephalomyelitis(EAE),which was induced by myelin oligodendrocyte glycoprotein 35–55 peptides.EAE mice showed decreased mean body weight but increased mean clinical scores compared with vehicle or control mice.And inflammatory infiltration was found in the lumbosacral spinal cord of EAE mice.In addition,VDR expression was significantly lower while the expression of miR-125a-5p was markedly higher in the spinal ventral horn of EAE mice than in vehicle or control mice.Importantly,activation of VDRs by paricalcitol or inhibition of miR-125a-5p by its antagomir markedly decreased the mean clinical scores in EAE mice.Interestingly,VDR and miR-125a-5p were co-localized in the same neurons of the ventral horn.More importantly,inhibition of miR-125a-5p remarkably blocked the decrease of VDRs in EAE mice.These results support a critical role for miR-125a-5p in modulating VDR activity in EAE and suggest potential novel therapeutic interventions.