Role of Wnt/PCP pathway on bronchial cell function in Idiopathic Pulmonary Fibrosis

Rationale: Idiopathic pulmonary fibrosis (IPF) is a devastating lung disorder of unknown etiology. IPF likely results from recurrent injury and impaired repair processes of epithelial cells. Within the epithelial cells, the re-activation of Wnt/β-catenin pathway has been demonstrated in alveolar and (peri)-bronchiolar regions. The non-canonical Wnt/Planar cell polarity pathway (Wnt/PCP) is important for epithelial cell movement and polarity generation. Recently, a novel PCP core components have been identified to be expressed in ciliated cells of the lung epithelium. Whether Wnt/PCP pathway is activated in epithelial cells, thereby contributing to lung fibrosis, remains unknown.

Methods: Gene expression profiling of Wnt/PCP components in tissue homogenates of experimental and human idiopathic pulmonary fibrosis was performed using qRT-PCR. C57BL/6 mice and Wnt/PCP deficient-mice were treated with bleomycin (5U/kg body weight) intratracheally using microsprayer, and survival was monitored over the period of 15 days post-bleo application. Further, fibrosis was characterized by examining lung function, lung histology (HE and Goldner staining), and immunofluorescence for β-tubulin and Wnt/PCP components.

Results: The Wnt/PCP components (such as Wnt5a, RhoA, Dvl2, Dvl3, Vangl2, Celsr1) were differenzially expressed both in experimental and human idiopathic pulmonary fibrosis. Wnt/PCP components localised to bronchial ciliated epithelial cells as determined by co-staining with β-tubulin. In the animal model, Wnt/PCP deficient-mice depicted altered lung histology, with airspace enlargement in alveolar regions compared with WT mice.

Discussion: Our data reveal a potential role of the Wnt/PCP pathway in bronchial epithelial cells in IPF. The Wnt/PCP pathway may be involved in the development of bronchial remodelling processes.