CIHR Group in Skeletal Development and Remodeling, Division of Oral Biology and Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, University of Western Ontario, Dental Sciences Building, London, ON, Canada, N6A 5C1.
J Cell Commun Signal. 2007 Dec;1(3-4):175-83. doi: 10.1007/s12079-007-0015-x. Epub 2008 Jan 20.
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 TGFbeta 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.
Wnt 蛋白在调节细胞分化、增殖和极性方面发挥着重要作用。有人提出 Wnt 在组织修复和纤维化中发挥作用，但尚未研究暴露于 Wnt 的成纤维细胞的基因表达谱。我们使用 Affymetrix 全基因组表达谱分析表明，Wnt3a 处理成纤维细胞 6 小时可诱导编码已知 Wnt 靶标的 mRNA 的表达，例如纤维生成性促黏附分子结缔组织生长因子 (CTGF，CCN2)。Wnt3a 还诱导编码强效促纤维化蛋白的 mRNAs，如 TGFβ 和内皮素-1 (ET-1)。此外，Wnt3a 促进与细胞黏附、迁移、血管生成发育、细胞增殖和 Wnt 信号转导相关的基因。相反，Wnt3a 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 Wnt3a 和 Wnt10b 的细胞的实时聚合酶链反应对结果进行了确认。这些结果表明，Wnt 诱导促进成纤维细胞向血管生成和基质重塑分化的基因，而牺牲骨骼发育。
