The major findings of our study are: (1) WNT5A is expressed very early by human airway epithelial cells and lung fibroblasts in response to LPS; (2) upregulation of WNT5A expression and non-phospho Ser33/37/Thr41 β-catenin are associated with upregulation of downstream target genes that are involved in profibrotic transformation of injured tissues, such as MMP7, cyclin D1 and VEGF; and (3) pulmonary fibrosis is induced very early during sepsis-induced ARDS, both experimentally and clinically. Here, VEGFA is linked to acute respiratory distress syndrome.