Department of Medicine, Division of Pulmonary and Critical Care Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
Curr Opin Rheumatol. 2011 Nov;23(6):562-7. doi: 10.1097/BOR.0b013e32834b3309.
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.
Wnt/β-连环蛋白信号通路在发育和成人组织稳态中发挥着关键作用。最近的研究表明 Wnt/β-连环蛋白信号通路参与了异常伤口修复和纤维化。本文旨在强调最近的关键研究，这些研究支持 Wnt/β-连环蛋白信号通路在纤维化中的作用。
纤维化疾病患者的研究表明，Wnt/β-连环蛋白通路的成分发生了变化。在动物模型中，Wnt/β-连环蛋白信号的干扰似乎加剧或改善了各种不同组织中损伤和纤维化的标志物。研究还表明，来自不同组织来源的成纤维细胞对 Wnt/β-连环蛋白信号的反应可能有很大的差异。Wnt/β-连环蛋白和转化生长因子-β信号通路之间的串扰是复杂的且依赖于背景，可能通过共同调控纤维生成基因靶点来促进纤维化。高通量筛选已经确定了几种新型的 Wnt/β-连环蛋白信号的化学抑制剂，这些抑制剂可能具有治疗潜力。
Wnt/β-连环蛋白信号在正常伤口愈合中很重要，其持续激活与纤维化有关。Wnt/β-连环蛋白信号调节对损伤反应的机制依赖于细胞类型和背景。更好地理解这一信号通路可能为人类纤维化疾病提供一种有前途的新治疗方法。
