Dual role of Response gene to complement-32 in multiple sclerosis

作者：Tegla Cosmin A; Cudrici Cornelia D; Azimzadeh Philippe; Singh Anil K; Trippe Richard III; Khan Ali; Chen Hegang; Andrian Albescu Maria; Royal Walter III; Bever Christopher; Rus Violeta; Rus Horea^*

来源：Experimental and Molecular Pathology, 2013, 94(1): 17-28.

DOI：10.1016/j.yexmp.2012.09.005

• RGC-32
• Multiple sclerosis
• Astrocyte
• Biomarker
• Gliosis
• Apoptosis

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 a-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.

• 出版日期2013-2