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

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.

Aquaporin-1 expression as an indicator in evaluating the efficacy of meloxicam in the treatment of ankylosing spondylitis: A comparative study.

OBJECTIVE: The key objective of the study was to investigate the correlation between the expression of aquaporin-1 (AQP1) and the efficacy of meloxicam and expressions of pro-inflammatory cytokines in ankylosing spondylitis (AS). METHODS: 40 AS patients whom had received meloxicam were recruited and subsequently placed into the experiment, while 40 healthy individuals were recruited as control group. Clinical indicators were detected before treatment (0 week), and at 2, 4, 6, 8, 10 and 12 week intervals after treatment, which included various assessments including Ankylosing Spondylitis 20% (ASAS20) response, Bath ankylosing spondylitis disease activity index (BASDAI), visual analog scale (VAS) for back pain, duration of morning stiffness, Bath ankylosing spondylitis functional index (BASFI), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) levels. Healthy volunteers were examined for ESR and CRP levels. The mRNA and protein expressions of AQP1 and pro-inflammatory cytokines, tumor necrosis factor-α (TNF-α) and interleukin-2 (IL-2), in peripheral blood mononuclear cells (PBMCs) were detected 6 and 12 weeks after treatment using reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blotting. Correlation of expressions of AQP1, efficacy of meloxicam and expression of pro-inflammatory cytokines were determined via Pearson correlation analysis. RESULTS: Following 12 weeks of meloxicam treatment, the ASAS20 response reached 93.7±3.61%. 6 weeks after treatment, BASDAI, VAS for back pain, duration of morning stiffness, BASFI, ESR, and CRP levels all exhibited considerably reduced levels compared to the initial levels observed prior to the commencement of treatment. Compared with before treatment, the expressions of TNF-α, IL-2 and AQP1 mRNA and protein all displayed decreases in the experiment group after both 6 and 12-week periods of treatment. Pre and post treatment levels of TNF-α, IL-2 and AQP1 mRNA and protein expressions were higher than those in the control group. The expressions of AQP1 mRNA and protein in the experiment group were positively correlated with clinical indicators and expressions of pro-inflammatory cytokines. CONCLUSION: Our findings indicated that AQP1 was both highly expressed and positively correlated with the efficacy of meloxicam and expressions of pro-inflammatory cytokines in AS patients, thereby highlighting the promise of meloxicam as a potential indicator in predicting the efficacy in the treatment of AS.