Wnts as essential growth factors for the adult small intestine and colon
Wnts as essential growth factors for the adult small intestine and colon
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DOI：
10.4161/cc.3.5.858
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发表时间：
2004-05-01
期刊：
影响因子：
4.3
通讯作者：
Kuo, CJ
中科院分区：
文献类型：
--
作者：
Hoffman, J;Kuhnert, F;Kuo, CJ
Wnt蛋白的生理功能的研究由于编码Wnt因子及其卷曲受体的家族的冗余性质而变得复杂。使用腺病毒表达分泌的Wnt拮抗剂Dickkopf-1（Dkk 1）来实现成年小鼠中经典Wnt信号传导的完全条件性抑制。Dkk 1的系统性表达导致Wnt靶基因表达和小肠和结肠增殖的快速抑制，增殖性隐窝的丧失，以及最终的炎症和结构退化。这些研究表明，在维持成人小肠和结肠增殖的细胞外Wnt信号的基本要求。Wnt信号传导在结肠持续增殖中的重要作用提示了炎症性肠病粘膜修复的潜在临床应用，并强调了腺病毒策略在成年生物体中有条件消融基因功能的实用性。
The study of physiologic functions of Wnt proteins has been complicated by the redundant nature of the families encoding the Wnt factors and their Frizzled receptors. Adenoviral expression of the secreted Wnt antagonist Dickkopf-1 (Dkk1) was used to achieve fully conditional inhibition of canonical Wnt signaling in adult mice. Systemic expression of Dkk1 resulted in rapid inhibition of Wnt target gene expression and of proliferation of the small intestine and colon, loss of proliferative crypts, and eventual inflammation and architectural degeneration. These studies indicate an essential requirement for extracellular Wnt signaling in the maintenance of adult small intestine and colon proliferation. The essential role of Wnt signaling in ongoing proliferation in the colon suggests potential clinical applications in mucosal repair for inflammatory bowel diseases and underscores the utility of adenoviral strategies for conditional ablation of gene function in adult organisms.