Dual role of Response gene to complement-32 in multiple sclerosis |
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Authors: | Cosmin A Tegla Cornelia D Cudrici Philippe Azimzadeh Anil K Singh Richard Trippe III Ali Khan Hegang Chen Maria Andrian-Albescu Walter Royal III Christopher Bever Violeta Rus Horea Rus |
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Institution: | 1. Department of Neurology, University of Maryland School of Medicine, Baltimore, MD, USA;2. Department of Medicine, Division of Rheumatology and Clinical Immunology, University of Maryland School of Medicine, Baltimore, MD, USA;3. Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, MD, USA;4. Research Service, Veterans Administration Maryland Health Care System, Baltimore, MD, USA;5. Veterans Administration Multiple Sclerosis Center of Excellence, Baltimore, MD, USA |
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Abstract: | Response gene to complement (RGC)-32 is a novel molecule that plays an important role in cell proliferation. We investigated the expression of RGC-32 in multiple sclerosis (MS) brain and in peripheral blood mononuclear cells (PBMCs) obtained from patients with relapsing–remitting multiple sclerosis. We found that CD3+, CD68+, and glial fibrillar acidic protein (GFAP)+ cells in MS plaques co-localized with RGC-32. Our results show a statistically significant decrease in RGC-32 mRNA expression in PBMCs during relapses when compared to the levels in stable MS patients. This decrease might be useful in predicting disease activity in patients with relapsing–remitting MS. RGC-32 expression was also correlated with that of FasL mRNA during relapses. FasL mRNA expression was significantly reduced after RGC-32 silencing, indicating a role for RGC-32 in the regulation of FasL expression. In addition, the expression of Akt1, cyclin D1, and IL-21 mRNA was significantly increased during MS relapses when compared to levels in healthy controls. Furthermore, we investigated the role of RGC-32 in TGF-β-induced extracellular matrix expression in astrocytes. Blockage of RGC-32 using small interfering RNA significantly inhibits TGF-β induction of procollagen I, fibronectin and of the reactive astrocyte marker α-smooth muscle actin (α-SMA). Our data suggest that RGC-32 plays a dual role in MS, both as a regulator of T-cells mediated apoptosis and as a promoter of TGF-β-mediated profibrotic effects in astrocytes. |
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Keywords: | RGC-32 Multiple sclerosis Astrocyte Biomarker Gliosis Apoptosis |
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