KCa1.1 Potassium Channels Regulate Key Proinflammatory and Invasive Properties of Fibroblast-like Synoviocytes in Rheumatoid Arthritis
KCa1.1 Potassium Channels Regulate Key Proinflammatory and Invasive Properties of Fibroblast-like Synoviocytes in Rheumatoid Arthritis
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DOI：
10.1074/jbc.m111.312264
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发表时间：
2012-02-03
影响因子：
4.8
通讯作者：
Beeton, Christine
中科院分区：
文献类型：
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作者：
Hu, Xueyou;Laragione, Teresina;Beeton, Christine
成纤维细胞样滑膜细胞（FLS）在类风湿关节炎（RA）的发病机制中起重要作用。钾通道在许多细胞功能中具有调节作用。我们已经确定了钙和电压门控KCa1.1通道（BK，Maxi-K，Slo 1，KCNMA 1）作为主要的钾通道表达在从RA患者分离的FLS（RA-FLS）的质膜。我们进一步表明，阻断该通道扰乱了细胞的钙稳态，抑制了增殖，VEGF，IL-8和pro-MMP-2的产生，以及RA-FLS的迁移和侵袭。我们的研究结果表明KCa1.1通道在RA-FLS功能中的调节作用，并建议该通道作为治疗RA的潜在靶点。
Fibroblast-like synoviocytes (FLS) play important roles in the pathogenesis of rheumatoid arthritis (RA). Potassium channels have regulatory roles in many cell functions. We have identified the calcium-and voltage-gated KCa1.1 channel (BK, Maxi-K, Slo1, KCNMA1) as the major potassium channel expressed at the plasma membrane of FLS isolated from patients with RA (RA-FLS). We further show that blocking this channel perturbs the calcium homeostasis of the cells and inhibits the proliferation, production of VEGF, IL-8, and pro-MMP-2, and migration and invasion of RA-FLS. Our findings indicate a regulatory role of KCa1.1 channels in RA-FLS function and suggest this channel as a potential target for the treatment of RA.