The gene expression profile induced by Wnt 3a in NIH 3T3 fibroblasts
The gene expression profile induced by Wnt 3a in NIH 3T3 fibroblasts
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DOI：
10.1007/s12079-007-0015-x
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发表时间：
2007-12-01
影响因子：
4.1
通讯作者：
Leask, Andrew
中科院分区：
文献类型：
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作者：
Chen, Shaoqiong;McLean, Sarah;Leask, Andrew
Wnt蛋白在调节细胞分化、增殖和极性方面发挥重要作用。Wnt已被提出在组织修复和纤维化中发挥作用，但暴露于Wnt的成纤维细胞的基因表达谱尚未被研究。我们使用Affyphin全基因组表达谱显示，Wnt 3a的成纤维细胞的6小时处理导致编码已知Wnt靶点的mRNA的诱导，例如纤维化前粘附分子结缔组织生长因子（CTGF，CCN 2）。Wnt 3a还诱导编码有效的促纤维化蛋白如TGF β和内皮素-I（ET-1）的mRNA。此外，Wnt 3a促进与细胞粘附和迁移、脉管系统发育、细胞增殖和Wnt信号传导相关的基因。相反，Wnt 3a抑制与骨骼发育、基质降解和细胞死亡相关的基因。使用暴露于Wnt 3a和Wnt 10 b的细胞的实时聚合酶链反应确认结果。这些结果表明，Wnt诱导基因促进成纤维细胞分化血管生成和基质重塑，以骨骼发育为代价。
Wnt proteins play important roles in regulating cell differentiation, proliferation and polarity. Wnts have been proposed to play roles in tissue repair and fibrosis, yet the gene expression profile of fibroblasts exposed to Wnts has not been examined. We use Affymetrix genome-wide expression profiling to show that a 6-h treatment of fibroblasts of Wnt3a results in the induction of mRNAs encoding known Wnt targets such as the fibrogenic pro-adhesive molecule connective tissue growth factor (CTGF, CCN2). Wnt3a also induces mRNAs encoding potent pro-fibrotic proteins such as TGF beta and endothelin-1 (ET-1). Moreover, Wnt3a promotes genes associated with cell adhesion and migration, vasculature development, cell proliferation and Wnt signaling. Conversely, Wnt3a suppresses gene associated with skeletal development, matrix degradation and cell death. Results were confirmed using real-time polymerase chain reaction of cells exposed to Wnt3a and Wnt10b. These results suggest that Wnts induce genes promoting fibroblast differentiation towards angiogenesis and matrix remodeling, at the expense of skeletal development.