Saturday, September 7, 2024
9/7/2024
Project Summary Idiopathic pulmonary fibrosis (IPF) is a fatal form of progressive lung fibrosis (scarring), resulting in a loss of 40,000 Americans a year - a number of deaths similar to that of breast cancer. The role of basal cells or basal- like cells in IPF is unknown. Basal cells are stem cells in the airway. However, accumulation of aberrant basal- like cells has been reported in IPF. Using the state-of-the-art technology, we identified that basal-like cells are significantly expanded in IPF lungs, and may have a pathological role. Furthermore, dysregulated signaling pathways in basal-like cells cause excessive production of WNT7A. Our preliminary studies showed that WNT7A promotes fibroblast activation and impairs renewal of type 2 alveolar epithelial stem cells (AT2). We therefore formed a unified hypothesis that the dysregulated signaling pathways in the pathogenically accumulated basal- like cells in IPF promote fibrogenesis by activation of the WNT signaling, leading to impairment of AT2 renewal and to exaggerated fibroblast activation. We will test this hypothesis in human samples collected from lung transplants and also in genetically modified mouse models. Therapeutic strategy to target WNT7A could improve alveolar progenitor activity and damper fibroblast activation, thus leading to alleviate lung injury and prevent lung fibrosis.
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