Department of Nephrology, Second Xiangya Hospital, Central South University, Changsha, PR China.
Physiol Res. 2012;61(4):337-46. doi: 10.33549/physiolres.932289. Epub 2012 Jun 6.
Wnt/beta-catenin signaling is involved in virtually every aspect of embryonic development and also controls homeostatic self-renewal in a number of adult tissues. Recently, emerging evidence from researches of organ fibrosis suggest that sustained Wnt/beta-catenin pathway reactivation is linked to the pathogenesis of fibrotic disorders. Here we focus on Wnt/beta-catenin-related pathogenic effects in different organs, such as lung fibrosis, liver fibrosis, skin fibrosis and renal fibrosis. Additionally, Wnt/beta-catenin signaling works in a combinatorial manner with TGF-beta signaling in the process of fibrosis, and TGF-beta signaling can induce expression of Wnt/beta-catenin superfamily members and vice versa. Moreover, network analysis, based on pathway databases, revealed that key factors in the Wnt pathway were targeted by some differentially expressed microRNAs detected in fibrosis diseases. These findings demonstrated the crosstalks between Wnt/beta-catenin pathway and TGF-beta signalings, and microRNAs, highlighting the role of Wnts in organ fibrogenesis. Most importantly, nowadays there is a variety of Wnt pathway inhibitors which give us the potential therapeutic feasibility, modulation of the Wnt pathway may, therefore, present as a suitable and promising therapeutic strategy in the future.
Wnt/β-连环蛋白信号通路参与胚胎发育的几乎所有方面，还能调控多种成年组织的稳态自我更新。最近，器官纤维化研究的新证据表明，持续的 Wnt/β-连环蛋白通路再激活与纤维化疾病的发病机制有关。本文主要聚焦于 Wnt/β-连环蛋白信号通路在不同器官中的致病效应，如肺纤维化、肝纤维化、皮肤纤维化和肾纤维化。此外，在纤维化过程中，Wnt/β-连环蛋白信号通路与 TGF-β信号通路以组合的方式发挥作用，TGF-β信号通路可以诱导 Wnt/β-连环蛋白超家族成员的表达，反之亦然。此外，基于通路数据库的网络分析显示，纤维化疾病中检测到的一些差异表达 microRNAs 靶向 Wnt 通路中的关键因子。这些发现表明 Wnt/β-连环蛋白通路和 TGF-β信号通路之间存在串扰，以及 microRNAs，强调了 Wnts 在器官纤维化发生中的作用。最重要的是，目前有多种 Wnt 通路抑制剂，这为我们提供了潜在的治疗可行性，因此，Wnt 通路的调节可能成为未来一种合适且有前景的治疗策略。
