The cation channel Trpv2 is a new suppressor of arthritis severity, joint damage, and synovial fibroblast invasion.
The cation channel Trpv2 is a new suppressor of arthritis severity, joint damage, and synovial fibroblast invasion.
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DOI：
10.1016/j.clim.2015.04.001
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发表时间：
2015-06
期刊：
影响因子：
--
通讯作者：
Gulko PS
中科院分区：
文献类型：
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作者：
Laragione T;Cheng KF;Tanner MR;He M;Beeton C;Al-Abed Y;Gulko PS
关于类风湿性关节炎(RA)的关节炎严重程度和关节损害的调节，人们知之甚少。成纤维细胞样滑膜细胞(FLS)在关节损伤中起核心作用，并表达高水平的阳离子通道Trpv2。我们的目标是确定Trpv2在关节炎中的作用。用Trpv2特异性激动剂治疗可降低RA患者以及关节炎大鼠和小鼠FLS的体外侵袭力。Trpv2刺激可抑制IL-1β诱导的MMP2和MMP3的表达。Trpv2激动剂，包括新的、更有效的LER13，显著降低了KRN血清和胶原诱导的关节炎的疾病严重程度，并减少了组织学关节损伤、滑膜炎症和滑膜血管数量，表明具有抗血管生成活性。在首次活体使用Trpv2激动剂时，我们发现了Trpv2在关节炎中的一个新的中心作用。这些新化合物有可能成为治疗类风湿性关节炎和其他与炎症、侵袭和血管生成相关的疾病的新疗法。
Little is known about the regulation of arthritis severity and joint damage in rheumatoid arthritis (RA). Fibroblast-like synoviocytes (FLS) have a central role in joint damage and express increased levels of the cation channel Trpv2. We aimed at determining the role of Trpv2 in arthritis. Treatment with Trpv2-specific agonists decreased the in vitro invasiveness of FLS from RA patients and arthritic rats and mice. Trpv2 stimulation suppressed IL-1β-induced expression of MMP-2 and MMP-3. Trpv2 agonists, including the new and more potent LER13, significantly reduced disease severity in KRN serum- and collagen-induced arthritis, and reduced histologic joint damage, synovial inflammation, and synovial blood vessel numbers suggesting anti-angiogenic activity. In this first in vivo use of Trpv2 agonists we discovered a new central role for Trpv2 in arthritis. These new compounds have the potential to become new therapies for RA and other diseases associated with inflammation, invasion and angiogenesis.