Wnt5a promotes adhesion of human dermal fibroblasts by triggering a phosphatidylinositol-3 kinase/Akt signal
Wnt5a promotes adhesion of human dermal fibroblasts by triggering a phosphatidylinositol-3 kinase/Akt signal
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DOI：
10.1016/j.cellsig.2007.07.023
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发表时间：
2007-12-01
影响因子：
4.8
通讯作者：
Matsuoka, Masaaki
中科院分区：
文献类型：
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作者：
Kawasaki, Aya;Torii, Kosuke;Matsuoka, Masaaki
Frizzled-3（Fzd 3）在中枢神经系统（CNS）和皮肤中高度表达，在CNS发育期间的轴突生长和引导中起重要作用，并且可能参与皮肤完整性的维持，尽管其配体仍未确定。在这项研究中，我们证明，Wnt 5a特异性结合Fzd 3在体外和触发磷酸化Akt介导的磷脂酰肌醇-3激酶（PI 3 K），但不是ERK或蛋白激酶C，在人原代培养的皮肤成纤维细胞。我们还发现，这种Wnt 5a/Fzd 3触发的PI 3 K/Akt信号的激活促进了整合素介导的人真皮成纤维细胞与胶原I包被的培养皿的粘附。基于Wnt 5a/Fzd 3触发的PI 3 K/Akt信号的激活被过量的重组Fzd 3-富含半胱氨酸的结构域（CRD）阻断，而不是被重组Fzd 6-CRD阻断的另一个发现，可以得出结论，Wnt 5a是Fzd 3的天然配体，其触发PI 3 K/Akt信号并促进人真皮成纤维细胞的粘附。(C)2007爱思唯尔公司All rights reserved.
Frizzled-3 (Fzd3), highly expressed in both the central nervous system (CNS) and skin, plays essential roles in axonal growth and guidance during the CNS development and may be involved in maintenance of skin integrity, although its ligand remains undetermined. In this study, we demonstrate that Wnt5a specifically binds to Fzd3 in vitro and triggers phosphorylation of Akt mediated by phosphatidylinositol-3 kinase (PI3K), but not that of ERK or protein kinase C, in human primary-cultured dermal fibroblasts. We have further found that such Wnt5a/Fzd3-triggered activation of the PI3K/Akt signal promotes integrin-mediated adhesion of human dermal fibroblasts to collagen I-coated dishes. Based on another finding that Wnt5a/Fzd3-triggered activation of the PI3K/Akt signal was blocked by an excess amount of a recombinant Fzd3-cysteine-rich domain (CRD), but not by that of a recombinant Fzd6-CRD, it is concluded that Wnt5a is a natural ligand of Fzd3 that triggers the PI3K/Akt signal and promotes adhesion of human dermal fibroblasts. (C) 2007 Elsevier Inc. All rights reserved.