WHAMM Inhibits Type II Alveolar Epithelial Cell EMT by Mediating Autophagic Degradation of TGF‐β1 in Bronchopulmonary Dysplasia

Bronchopulmonary dysplasia (BPD) is one of the most prevalent complication in preterm infants, primarily characterized by arrested alveolar growth. The involvement of epithelial-mesenchymal transition (EMT) of AECII cells is proposed to have a crucial role in the pathogenesis of BPD; however, the underlying mechanism remains unclear. The present study reveals a significant reduction of WHAMM (WASP homolog associated with actin, membranes, and microtubules) in hyperoxia-induced BPD mice, highlighting its crucial role in suppressing the progression of BPD through the inhibition of EMT in AECIIs. We demonstrated that hyperoxia-induced downregulation of WHAMM leads to the accumulation of TGF-β1 primarily through its mediation of the autophagic degradation pathway. Mechanistically, WHAMM enhanced the autophagosomal localization of TGF-β1 and concurrently promoted the process of autophagy, thereby comprehensively facilitating the autophagic degradation of TGF-β1. These findings reveal the important role of WHAMM in the development of BPD, and the proposed WHAMM/autophagy/TGF-β1/EMT pathway may represent a potential therapeutic strategy for BPD treatment.