Wnt signaling pathway in aging-related tissue fibrosis and therapies

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.