β-catenin signaling: a novel mediator of fibrosis and potential therapeutic target.

PURPOSE OF REVIEW: 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. RECENT
FINDINGS: 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.
SUMMARY: 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.