AKT Signaling Differentially Regulates the Expression of Two Evolutionarily Conserved Wnt5a Isoforms in Lung...

WNT5a is a lipid-modified glycoprotein member of the WNT family of signaling molecules. Two isoforms of WNT5a have been identified that are conserved across mice and humans. These isoforms display specific functions in regulating cancer cell activities. While WNT5a is, indeed, essential for normal lung development and homeostasis, and is dysregulated in multiple lung diseases, little to no information is available regarding the expression or potential function of WNT5a isoforms in normal or diseased lungs. Such information has the potential to help to elucidate the more precise and nuanced functions of WNT5a in various pulmonary conditions. In this study, we characterized the expression of individual Wnt5a isoforms during mouse lung development and compared their expression across major alveolar cell populations. We further investigated the molecular basis of the signaling mechanisms that regulate Wnt5a isoform expression in fibroblasts, the major lung cell type with high-level Wnt5a expression. We present data that reveal a role for the AKT pathway in differentially regulating the expression of Wnt5a isoforms, a novel finding. Furthermore, we demonstrate that Wnt5a isoforms are dysregulated in bleomycin-induced fibrosis and Pseudomonas aeruginosa (PA)-induced acute lung injury and exhibit distinct impacts in Wnt5a isoform expression in response to lung injury.