The Potential of WNT/B-Catenin Modulation in Treating Pulmonary Fibrosis

Pulmonary fibrosis, particularly idiopathic pulmonary fibrosis (IPF), represents a significant challenge in healthcare due to its detrimental impact on lung function and limited treatment options. While WNT/β-catenin signaling plays a crucial role in lung development and maintenance of adult lung stem cells, its dysregulation has been associated with pulmonary fibrosis. However, recent research has revealed a potential therapeutic avenue through the modulation of this signaling pathway.

WNT ligands bind to Frizzled (FZD) and LRP receptors, initiating canonical WNT/β-catenin signaling. Additionally, RSPO enhances this signaling by removing surface E3 ubiquitin ligases, which would otherwise target WNT receptors for degradation. Recent developments in antibody-based modulators of WNT signaling have shown promise in promoting tissue repair in various organ damages. Particularly, a multi-FZD-specific WNT mimetic demonstrated the expansion of alveolar cells in vitro, sparking interest in its therapeutic potential for pulmonary fibrosis.