title: Dual role of Response gene to complement-32 in multiple sclerosis.
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.
authors.affiliation: Department of Neurology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
authors.forename: Cosmin A
authors.initials: CA
authors.lastname: Tegla
authors.forename: Cornelia D
authors.initials: CD
authors.lastname: Cudrici
authors.forename: Philippe
authors.initials: P
authors.lastname: Azimzadeh
authors.forename: Anil K
authors.initials: AK
authors.lastname: Singh
authors.forename: Richard
authors.initials: R
authors.lastname: Trippe
authors.forename: Ali
authors.initials: A
authors.lastname: Khan
authors.forename: Hegang
authors.initials: H
authors.lastname: Chen
authors.forename: Maria
authors.initials: M
authors.lastname: Andrian-Albescu
authors.forename: Walter
authors.initials: W
authors.lastname: Royal
authors.forename: Christopher
authors.initials: C
authors.lastname: Bever
authors.forename: Violeta
authors.initials: V
authors.lastname: Rus
authors.forename: Horea
authors.initials: H
authors.lastname: Rus
mesh_terms: D000199:Actins / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000032:analysis; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis; D017209:Apoptosis; D001253:Astrocytes / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D017252:CD3 Complex / Q000032:analysis; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation; D024042:Collagen Type I / Q000378:metabolism; D003165:Complement System Proteins / Q000378:metabolism; D019938:Cyclin D1 / Q000096:biosynthesis / Q000235:genetics; D005109:Extracellular Matrix / Q000378:metabolism; D053222:Fas Ligand Protein / Q000235:genetics; D005260:Female; D005353:Fibronectins / Q000378:metabolism; D005904:Glial Fibrillary Acidic Protein; D006801:Humans; D007378:Interleukins / Q000096:biosynthesis / Q000235:genetics; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000378:metabolism*; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000096:biosynthesis / Q000235:genetics; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering; D013601:T-Lymphocytes / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism; D055815:Young Adult; D000098546:Interleukin-21; D000097382:CD68 Molecule
chemical_list: D000199:Actins; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D017252:CD3 Complex; D018797:Cell Cycle Proteins; D024042:Collagen Type I; D003165:Complement System Proteins; D019938:Cyclin D1; D053222:Fas Ligand Protein; D005353:Fibronectins; D005904:Glial Fibrillary Acidic Protein; D007378:Interleukins; D009124:Muscle Proteins; D009419:Nerve Tissue Proteins; D051057:Proto-Oncogene Proteins c-akt; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D016212:Transforming Growth Factor beta; D000098546:Interleukin-21; C541116:ACTA2 protein, human; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C505661:FASLG protein, human; C115049:RGCC protein, human; C514862:Akt1 protein, mouse