Wnt signaling induces matrix metalloproteinase expression and regulates T cell transmigration
Wnt signaling induces matrix metalloproteinase expression and regulates T cell transmigration
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DOI：
10.1016/j.immuni.2006.12.007
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发表时间：
2007-02-01
期刊：
影响因子：
32.4
通讯作者：
Hughes, Christopher C. W.
中科院分区：
文献类型：
--
作者：
Wu, Beibei;Crampton, Steve P.;Hughes, Christopher C. W.
Wnt是一个分泌性糖蛋白家族，具有多种发育作用，包括调节细胞迁移;然而，对成熟T细胞中的Wnt信号传导知之甚少。我们发现内皮细胞衍生的wnt通过Frizzled受体作用，诱导效应T细胞中基质金属蛋白酶（MMP）2和MMP 9的表达。阻断wnt信号传导或MMP活性可减少T细胞通过体外基底膜和体内炎症皮肤的迁移。Wnt信号转导稳定T细胞中的β-连环蛋白，并通过串联TCF位点直接靶向MMP启动子。因此，我们的数据支持必要的和以前意想不到的作用wnt信号在T细胞外渗。
Wnts are a family of secreted glycoproteins with diverse developmental roles, including regulation of cell migration; however, little is known about wnt signaling in mature T cells. We find that endothelial-cell-derived wnts, acting through Frizzled receptors, induce matrix metalloproteinase (MMP) 2 and MMP9 expression in effector T cells. Blocking wnt signaling, or MMP activity, reduces T cell migration through the basement membrane in vitro and into inflamed skin in vivo. Wnt signaling stabilizes beta-catenin protein in T cells and directly targets the MMP promoters through tandem TCF sites. Thus, our data support a necessary and previously unexpected role for wnt signaling in T cell extravasation.