Wang Y, Li Y, He Y, Sun Y, Sun W, Xie Q, Yin G, Du Y, Wang L, Shi G
Division of Rheumatology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, ChinaGLP Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
Scand J Immunol. 2012 Feb;75(2):203-9. doi: 10.1111/j.1365-3083.2011.02635.x.
Gαq, the alpha subunit of Gq, a member of the Gq/11 sub-family, was reported to inhibit phosphatidylinositol-3-Kinase (PI3K) activation and prevent the activation of Akt. Previous studies demonstrated that mice losing Gαq in their immune system could spontaneously develop inflammatory arthritis. In this study, we showed that the Gαq expressions at mRNA and protein levels in the peripheral blood lymphocytes (PBLs) from patients with rheumatoid arthritis (RA) were significantly decreased in comparison of which in healthy individuals. The expression levels of Gαq mRNA in PBLs from patients with RA were correlated with RA disease activity (DAS28), anti-cyclic citrullinated protein antibodies, C-reactive protein and rheumatoid factor. We also demonstrated that Gαq controlled the apoptosis of RA PBLs through regulating the activity of Mcl-1 and caspase-3. These data suggested that Gαq might be involved in the pathogenesis of RA by regulating PBLs apoptosis.
Gαq是Gq/11亚家族成员Gq的α亚基，据报道它可抑制磷脂酰肌醇-3-激酶（PI3K）的激活并阻止Akt的激活。先前的研究表明，免疫系统中缺失Gαq的小鼠会自发发展为炎性关节炎。在本研究中，我们发现，与健康个体相比，类风湿关节炎（RA）患者外周血淋巴细胞（PBL）中Gαq的mRNA和蛋白水平显著降低。RA患者PBL中Gαq mRNA的表达水平与RA疾病活动度（DAS28）、抗环瓜氨酸化蛋白抗体、C反应蛋白和类风湿因子相关。我们还证明，Gαq通过调节Mcl-1和caspase-3的活性来控制RA PBL的凋亡。这些数据表明，Gαq可能通过调节PBL凋亡参与RA的发病机制。
