AXL-GAS6/PROS1 Interaction: A Critical Switch Between Aberrant- and Healthy Repair Following Alveolar Lung Injury
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Previous studies have shown that altered AXL signaling is implicated in various diseases, with GAS6 recognized as its only relevant ligand to date. In this study, we show for the first-time a direct interaction between AXL and PROS1 using biochemical methods. Furthermore, we validate the biological significance of PROS1-AXL interaction through advanced quantitative and functional spatial imaging in both murine lung tissue, as well as human lung samples of idiopathic pulmonary fibrosis (IPF) patients. Our findings reveal the role of AXL-mediated biology in alveolar repair and the fibrotic response driven by GAS6 as well as PROS1. Notably, this effect involves PROS1 interacting with AXL to counteract GAS6 mediated effects. Together with the distinct temporal expression of profibrotic genes and the interplay between AXL and TGF-ß pathway, this emphasizes the potential of targeting AXL mediated biology for therapeutic intervention in IPF to allow alveolar restoration.
