Department of Internal Medicine 3, Institute for Clinical Immunology, University of Erlangen-Nuremberg, Erlangen, Germany.
Exp Dermatol. 2013 Nov;22(11):710-3. doi: 10.1111/exd.12255.
Canonical Wnt signalling belongs to the so-called morphogen pathways and plays essential roles in development and tissue homeostasis. Being such a crucial regulatory pathway, Wnt signalling is tightly controlled at different levels. However, uncontrolled activation of canonical Wnt signalling has been implicated into the pathogenesis of various human disorders. In the last years, aberrant Wnt signalling has been demonstrated in fibrotic diseases including systemic sclerosis (SSc). In this review, we will discuss the current state of research on canonical Wnt signalling in SSc. Activation of canonical Wnt signalling induces fibroblast activation with subsequent myofibroblast differentiation and excessive collagen release resulting in tissue fibrosis. Genetic or pharmacological blockade of Wnt activation ameliorates experimental fibrosis in different preclinical models. These findings have direct translational implications because several small molecule inhibitors of Wnt signalling are currently evaluated in clinical trials and some already showed first promising results.
经典 Wnt 信号通路属于所谓的形态发生途径，在发育和组织稳态中发挥着重要作用。作为如此关键的调节途径，Wnt 信号通路在不同水平受到严格控制。然而，经典 Wnt 信号通路的失控激活已被牵连到各种人类疾病的发病机制中。在过去的几年中，异常的 Wnt 信号通路已在包括系统性硬皮病 (SSc) 在内的纤维化疾病中得到证实。在这篇综述中，我们将讨论经典 Wnt 信号通路在 SSc 中的研究现状。经典 Wnt 信号通路的激活诱导成纤维细胞活化，随后肌成纤维细胞分化和过度胶原释放导致组织纤维化。Wnt 激活的遗传或药理学阻断可改善不同临床前模型中的实验性纤维化。这些发现具有直接的转化意义，因为目前正在临床试验中评估几种 Wnt 信号小分子抑制剂，其中一些已经显示出初步的有前景的结果。
