β-catenin signaling: a novel mediator of fibrosis and potential therapeutic target.
β-catenin signaling: a novel mediator of fibrosis and potential therapeutic target.
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DOI：
10.1097/bor.0b013e32834b3309
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发表时间：
2011-11
影响因子：
5.1
通讯作者：
Gottardi CJ
中科院分区：
文献类型：
--
作者：
Lam AP;Gottardi CJ
Wnt/β-catenin信号通路在发育和成体组织稳态中起关键作用。最近的研究表明Wnt/β-catenin信号在异常伤口修复和纤维形成中起作用。本综述的目的是强调最近支持Wnt/β-catenin信号在纤维化中的作用的关键研究。对纤维化疾病患者的研究表明Wnt/β-catenin通路成分发生了变化。在动物模型中，Wnt/β-catenin信号的扰动似乎会加重或改善多种不同组织中的损伤和纤维化标志物。研究还表明，来自不同组织来源的成纤维细胞对Wnt/β-catenin信号的反应可能存在明显差异。Wnt/β-catenin与转化生长因子-β信号通路之间的相互作用是复杂且依赖于环境的，可能通过纤维生成基因靶点的协同调节来促进纤维生成。高通量筛选已经确定了几种可能具有治疗潜力的Wnt/β-catenin信号传导的新型化学抑制剂。Wnt/β-连环蛋白信号在正常伤口愈合中显得很重要，其持续激活与纤维形成有关。Wnt/β-catenin信号可能改变损伤反应的机制是细胞类型和环境相关的。更好地了解这一信号通路可能为人类纤维化疾病的治疗提供一个有希望的新途径。
The Wnt/β-catenin signaling pathway plays a critical role in development and adult tissue homeostasis. Recent investigations implicate Wnt/β-catenin signaling in abnormal wound repair and fibrogenesis. The purpose of this review is to highlight recent key studies that support a role for Wnt/β-catenin signaling in fibrosis. Studies of patients with fibrotic diseases have demonstrated changes in components of the Wnt/β-catenin pathway. In animal models, perturbations in Wnt/β-catenin signaling appear to aggravate or ameliorate markers of injury and fibrosis in a variety of different tissues. Studies also suggest that fibroblasts from different tissue sources may have markedly divergent responses to Wnt/β-catenin signaling. Cross-talk between Wnt/β-catenin and transforming growth factor-β pathways is complex and context-dependent, and may promote fibrogenesis through coregulation of fibrogenic gene targets. High throughput screening has identified several novel chemical inhibitors of Wnt/β-catenin signaling that may be of therapeutic potential. Wnt/β-catenin signaling appears important in normal wound healing and its sustained activation is associated with fibrogenesis. The mechanism by which Wnt/β-catenin signaling may modify the response to injury is cell-type and context-dependent. Better understanding of this signaling pathway may provide a promising new therapeutic approach for human fibrotic diseases.