Transforming growth factor-β inhibits alveolar epithelial protein transport by glycogen synthase kinase 3-β-mediated downregulation of megalin

A hallmark of acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is the accumulation of protein-rich edema fluid in the distal airspaces removal of which is critical for patient survival. We have previously shown that albumin transport across the alveolar epithelial barrier is an active process mediated by megalin. Here we set out to identify the mechanisms that may impair megalin function upon ALI/ARDS. Particularly, we investigated the role of glycogen synthase kinase 3-β (GSK3-β), a serine-threonine kinase that is involved in various inflammatory disorders and that has been proposed to phosphory…