1. MiR-125a-5p Regulates Vitamin D Receptor Expression in a Mouse Model of Experimental Autoimmune Encephalomyelitis
- Author
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Dian He, Bing Shao, Chun-Feng Liu, Fei-Long Xiong, Ping-An Zhang, Zu Xu, Yifan Zhang, Rui Wu, Lan Chu, Han-Chun Long, and Guang-Yin Xu
- Subjects
0301 basic medicine ,Paricalcitol ,medicine.medical_specialty ,Encephalomyelitis, Autoimmune, Experimental ,Multiple Sclerosis ,Physiology ,Central nervous system ,Calcitriol receptor ,Myelin oligodendrocyte glycoprotein ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,microRNA ,Animals ,Medicine ,biology ,business.industry ,General Neuroscience ,Multiple sclerosis ,Experimental autoimmune encephalomyelitis ,Lumbosacral Region ,Spinal Cord Ventral Horn ,General Medicine ,medicine.disease ,Mice, Inbred C57BL ,MicroRNAs ,030104 developmental biology ,Endocrinology ,medicine.anatomical_structure ,Mechanism of action ,biology.protein ,Receptors, Calcitriol ,Female ,Original Article ,medicine.symptom ,business ,030217 neurology & neurosurgery ,medicine.drug - Abstract
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.
- Published
- 2019