Inhibition of Wnt10b/β-catenin signaling alleviates pulmonary fibrogenesis induced by paraquat in vivo and in vitro

Pulmonary fibrosis (PF) caused by paraquat remains a critical issue, and the molecular mechanisms are still unclear. Epithelial-mesenchymal transition (EMT) is regarded as a hallmark of PF, conferring alveolar epithelial cells partial mesenchymal characteristics, facilitating migration, expressing excessive extracellular matrix components, and participating in lung parenchyma remodeling and stiffening. Aberration of Wnt signaling has been identified in EMT and PF, and Wnt protein family consists of 19 ligands. The relationship of the specific Wnt ligands and fibrogenesis induced by PQ was not well defined. In current study, PQ-induced lung fibrosis rat model and EMT cell model were utilized to investigate the underlying molecular mechanisms both in vivo and in vitro. The results demonstrated that canonical Wnt/β-catenin signaling was highly activated and Wnt10b was the most affected. Additionally, suppression of Wnt10b by RNA interference could reverse EMT in vitro and detain the process of PF in vivo. These data establish Wnt10b as the key regulator of EMT and lung fibrogenesis, and suggest the potential of targeted interference against Wnt10b as a promising therapeutic strategy for lung fibrosis.