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.
Copyright © 2012 Elsevier Inc. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Actins / metabolism
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Adolescent
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Adult
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Aged
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Antigens, CD / analysis
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Antigens, Differentiation, Myelomonocytic / analysis
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Apoptosis
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Astrocytes / metabolism
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Brain / metabolism*
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CD3 Complex / analysis
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Cell Cycle Proteins / genetics
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Cell Cycle Proteins / metabolism*
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Cell Proliferation
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Collagen Type I / metabolism
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Complement System Proteins / metabolism
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Cyclin D1 / biosynthesis
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Cyclin D1 / genetics
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Extracellular Matrix / metabolism
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Fas Ligand Protein / genetics
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Female
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Fibronectins / metabolism
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Glial Fibrillary Acidic Protein
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Humans
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Interleukins / biosynthesis
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Interleukins / genetics
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Leukocytes, Mononuclear / metabolism*
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Male
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Middle Aged
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Multiple Sclerosis, Relapsing-Remitting / metabolism*
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Muscle Proteins / genetics
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Muscle Proteins / metabolism*
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / metabolism*
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Proto-Oncogene Proteins c-akt / biosynthesis
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Proto-Oncogene Proteins c-akt / genetics
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RNA Interference
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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RNA, Small Interfering
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T-Lymphocytes / metabolism
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Transforming Growth Factor beta / metabolism
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Young Adult
Substances
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ACTA2 protein, human
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Actins
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Antigens, CD
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Antigens, Differentiation, Myelomonocytic
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CD3 Complex
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CD68 antigen, human
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Cell Cycle Proteins
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Collagen Type I
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FASLG protein, human
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Fas Ligand Protein
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Fibronectins
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Glial Fibrillary Acidic Protein
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Interleukins
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Muscle Proteins
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Nerve Tissue Proteins
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RGCC protein, human
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RNA, Messenger
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RNA, Small Interfering
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Transforming Growth Factor beta
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Cyclin D1
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Complement System Proteins
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Akt1 protein, mouse
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Proto-Oncogene Proteins c-akt
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interleukin-21