Wnt5A regulates specific targets in canonical and non-canonical Wnt pathways in alveolar type II epithelial cells through an lncRNA-mRNA co-expression network

Bronchopulmonary dysplasia (BPD) is a major respiratory complication in preterm infants, characterized by impaired alveolarization. While Wnt5A, a non-canonical Wnt ligand, is upregulated in BPD, its specific role in alveolar type II epithelial cells, the key progenitors for lung repair, remains unclear. This study investigated how Wnt5A regulates the balance between canonical and non-canonical Wnt signaling in AT2 cells. We constructed an lncRNA-mRNA co-expression network by integrating transcriptomic data from MLE-12 cells subjected to hyperoxia or Wnt5A overexpression. Our results demonstrate that Wnt5A acts as a critical node that disrupts Wnt signaling homeostasis, promoting non-canonical pathways while inhibiting the canonical branch, which aligns with impaired cell proliferation and increased apoptosis. Crucially, the network analysis identified several high-confidence lncRNA-mRNA regulatory pairs, including Kcnq1ot1-Ccnd1 and, most notably, Gm12781-Wnt5A, which exhibits a positive correlation suggestive of a novel positive feedback loop. These findings provide a new molecular map of Wnt5A's function in alveolar injury, highlighting specific lncRNAs as potential mediators and therapeutic targets for intervening in the dysregulated Wnt signaling that underlies BPD pathogenesis.