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Wnt signaling pathway in aging-related tissue fibrosis and therapies.
Ageing Research Reviews ( IF 12.5 ) Pub Date : 2020-04-06 , DOI: 10.1016/j.arr.2020.101063
He-He Hu 1 , Gang Cao 2 , Xia-Qing Wu 1 , Nosratola D Vaziri 3 , Ying-Yong Zhao 1
Affiliation  

Fibrosis is the final hallmark of pathological remodeling, which is a major contributor to the pathogenesis of various chronic diseases and aging-related organ failure to fully control chronic wound-healing and restoring tissue function. The process of fibrosis is involved in the pathogenesis of the kidney, lung, liver, heart and other tissue disorders. Wnt is a highly conserved signaling in the aberrant wound repair and fibrogenesis, and sustained Wnt activation is correlated with the pathogenesis of fibrosis. In particular, mounting evidence has revealed that Wnt signaling played important roles in cell fate determination, proliferation and cell polarity establishment. The expression and distribution of Wnt signaling in different tissues vary with age, and these changes have key effects on maintaining tissue homeostasis. In this review, we first describe the major constituents of the Wnt signaling and their regulation functions. Subsequently, we summarize the dysregulation of Wnt signaling in aging-related fibrotic tissues such as kidney, liver, lung and cardiac fibrosis, followed by a detailed discussion of its involvement in organ fibrosis. In addition, the crosstalk between Wnt signaling and other pathways has the potential to profoundly add to the complexity of organ fibrosis. Increasing studies have demonstrated that a number of Wnt inhibitors had the potential role against tissue fibrosis, specifically in kidney fibrosis and the implications of Wnt signaling in aging-related diseases. Therefore, targeting Wnt signaling might be a novel and promising therapeutic strategy against aging-related tissue fibrosis.



中文翻译:

Wnt信号通路在衰老相关的组织纤维化和治疗中。

纤维化是病理重塑的最后标志,它是各种慢性疾病和衰老相关器官衰竭的发病机理,从而无法完全控制慢性伤口愈合和恢复组织功能,这是主要原因。纤维化的过程涉及肾脏,肺,肝,心脏和其他组织疾病的发病机理。Wnt在异常的伤口修复和纤维形成中是高度保守的信号,并且持续的Wnt活化与纤维化的发病机理相关。特别是,越来越多的证据表明Wnt信号在细胞命运决定,增殖和细胞极性建立中起着重要作用。Wnt信号在不同组织中的表达和分布随年龄变化,这些变化对维持组织稳态具有关键作用。在这篇评论中 我们首先描述Wnt信号的主要成分及其调控功能。随后,我们总结了与衰老相关的纤维化组织(例如肾,肝,肺和心脏纤维化)中Wnt信号的失调,然后详细讨论了其参与器官纤维化的过程。此外,Wnt信号传导和其他途径之间的串扰可能会大大增加器官纤维化的复杂性。越来越多的研究表明,许多Wnt抑制剂具有抗组织纤维化的潜在作用,特别是在肾脏纤维化中以及Wnt信号转导与衰老相关的疾病中。因此,靶向Wnt信号传导可能是对抗衰老相关组织纤维化的新颖且有希望的治疗策略。

更新日期:2020-04-06
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