QKI-V5 is downregulated in CNS inflammatory demyelinating diseases
Iris Lavon1, Ina Leykin1, Hanna Charbit1
1Department of Neurology, the Agnes-Ginges Center for Neurogenetics, Hadassah- Medical Center, Hebrew University, Jerusalem, Israel; Leslie and Michael Center for Neuro-oncology, Hadassah-Medical Center, Jerusalem, Israel.
Background:
Neuromyelitis-optica (NMO) and multiple-sclerosis (MS) are inflammatory- demyelinating-diseases of the central-nervous-system (CNS). In a previous study, we identified 17 miRNAs that were significantly upregulated in the peripheral blood of patients with NMO, relative to healthy controls (HCs). Target gene analysis have demonstrated that QKI is targeted by 70% of the upregulated miRNAs. QKI gene encodes for a RNA-binding-protein that plays a central role in myelination. QKI variants 5, 6, 7 (QKI-V5, QKI-V6, QKI-V7) are generated via alternative splicing. Given the role played by QKI in myelination we aimed to study the expression levels of QKI variants in the circulation of patients with NMO and MS and in the circulation and brain tissue of mice-model to CNS-inflammatory-demyelinating-disease.
Methods:
RNA and protein expression levels of QKI variants QKI-V5, QKI-V6 and QKI-V7 were determined in the blood of patients with NMO (n = 23) or MS (n = 13). The effect of sera from patients on the expression of QKI in normal peripheral-blood-mononuclear-cells (PBMCs) or glial cells was explored. The mog-experimental-autoimmune-encephalomyelitis (EAE) mouse model was used to study the correlation between the changes in the expression levels of QKI in the blood to those in the brain.
Results:
RNA and protein expression of QKI-V5 was decreased in the peripheral blood of patients with NMO and multiple-sclerosis. Incubation of normal peripheral-blood-mononuclear-cells or glial cells with sera of patients significantly reduced the expression of QKI-V5. The blood and brain of EAE mice exhibited a corresponding decrease in QKI-V5 expression.
Conclusion:
The downregulation in the expression of QKI-V5 in the blood of patients with CNS-inflammatory-demyelinating-diseases and in the brain and blood of EAE mice is likely caused by a circulating factor and might promote re-myelination by regulation of myelin-associated genes.
Key Words:
QKI variants, Multiple sclerosis (MS), Neuromyelitis optica (NMO), Astrocytes, Demyelination.
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