PMID- 23000427 OWN - NLM STAT- MEDLINE DCOM- 20130403 LR - 20211021 IS - 1096-0945 (Electronic) IS - 0014-4800 (Linking) VI - 94 IP - 1 DP - 2013 Feb TI - Dual role of Response gene to complement-32 in multiple sclerosis. PG - 17-28 LID - S0014-4800(12)00127-X [pii] LID - 10.1016/j.yexmp.2012.09.005 [doi] AB - 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-beta-induced extracellular matrix expression in astrocytes. Blockage of RGC-32 using small interfering RNA significantly inhibits TGF-beta induction of procollagen I, fibronectin and of the reactive astrocyte marker alpha-smooth muscle actin (alpha-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-beta-mediated profibrotic effects in astrocytes. CI - Copyright (c) 2012 Elsevier Inc. All rights reserved. FAU - Tegla, Cosmin A AU - Tegla CA AD - Department of Neurology, University of Maryland School of Medicine, Baltimore, MD 21201, USA. FAU - Cudrici, Cornelia D AU - Cudrici CD FAU - Azimzadeh, Philippe AU - Azimzadeh P FAU - Singh, Anil K AU - Singh AK FAU - Trippe, Richard 3rd AU - Trippe R 3rd FAU - Khan, Ali AU - Khan A FAU - Chen, Hegang AU - Chen H FAU - Andrian-Albescu, Maria AU - Andrian-Albescu M FAU - Royal, Walter 3rd AU - Royal W 3rd FAU - Bever, Christopher AU - Bever C FAU - Rus, Violeta AU - Rus V FAU - Rus, Horea AU - Rus H LA - eng GR - I01 BX001458/BX/BLRD VA/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20120919 PL - Netherlands TA - Exp Mol Pathol JT - Experimental and molecular pathology JID - 0370711 RN - 0 (ACTA2 protein, human) RN - 0 (Actins) RN - 0 (Antigens, CD) RN - 0 (Antigens, Differentiation, Myelomonocytic) RN - 0 (CD3 Complex) RN - 0 (CD68 antigen, human) RN - 0 (Cell Cycle Proteins) RN - 0 (Collagen Type I) RN - 0 (FASLG protein, human) RN - 0 (Fas Ligand Protein) RN - 0 (Fibronectins) RN - 0 (Glial Fibrillary Acidic Protein) RN - 0 (Interleukins) RN - 0 (Muscle Proteins) RN - 0 (Nerve Tissue Proteins) RN - 0 (RGCC protein, human) RN - 0 (RNA, Messenger) RN - 0 (RNA, Small Interfering) RN - 0 (Transforming Growth Factor beta) RN - 136601-57-5 (Cyclin D1) RN - 9007-36-7 (Complement System Proteins) RN - EC 2.7.11.1 (Akt1 protein, mouse) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - MKM3CA6LT1 (interleukin-21) SB - IM MH - Actins/metabolism MH - Adolescent MH - Adult MH - Aged MH - Antigens, CD/analysis MH - Antigens, Differentiation, Myelomonocytic/analysis MH - Apoptosis MH - Astrocytes/metabolism MH - Brain/*metabolism MH - CD3 Complex/analysis MH - Cell Cycle Proteins/genetics/*metabolism MH - Cell Proliferation MH - Collagen Type I/metabolism MH - Complement System Proteins/metabolism MH - Cyclin D1/biosynthesis/genetics MH - Extracellular Matrix/metabolism MH - Fas Ligand Protein/genetics MH - Female MH - Fibronectins/metabolism MH - Glial Fibrillary Acidic Protein MH - Humans MH - Interleukins/biosynthesis/genetics MH - Leukocytes, Mononuclear/*metabolism MH - Male MH - Middle Aged MH - Multiple Sclerosis, Relapsing-Remitting/*metabolism MH - Muscle Proteins/genetics/*metabolism MH - Nerve Tissue Proteins/genetics/*metabolism MH - Proto-Oncogene Proteins c-akt/biosynthesis/genetics MH - RNA Interference MH - RNA, Messenger/genetics/metabolism MH - RNA, Small Interfering MH - T-Lymphocytes/metabolism MH - Transforming Growth Factor beta/metabolism MH - Young Adult EDAT- 2012/09/25 06:00 MHDA- 2013/04/04 06:00 CRDT- 2012/09/25 06:00 PHST- 2012/07/25 00:00 [received] PHST- 2012/09/10 00:00 [accepted] PHST- 2012/09/25 06:00 [entrez] PHST- 2012/09/25 06:00 [pubmed] PHST- 2013/04/04 06:00 [medline] AID - S0014-4800(12)00127-X [pii] AID - 10.1016/j.yexmp.2012.09.005 [doi] PST - ppublish SO - Exp Mol Pathol. 2013 Feb;94(1):17-28. doi: 10.1016/j.yexmp.2012.09.005. Epub 2012 Sep 19.