YAP and Wnt3a independently promote AECIIs proliferation and differentiation by increasing nuclear β-catenin expression in experimental bronchopulmonary dysplasia

Abstract

Arrested alveolar development is the main pathological characteristic of neonatal bronchopulmonary dysplasia (BPD); however, a number of studies aiming to improve alveolarization have focused on alveolar epithelial cell damage and impairment. Previously, the authors reported that the Wnt signaling plays a key role in alveolar injury and repair by regulating alveolar epithelial type II cell (AECII) proliferation and differentiation. In the present study, the authors wished to investigate whether Yes-associated protein (YAP), a transcriptional coactivator in the Hippo signaling pathway, affects AEcII proliferation and differentiation via the Wnt/β-catenin pathway in BPd. It was found that YAP regulated AEcII proliferation and differentiation. A decreased expression of YAP, Wnt3a and nuclear β-catenin was observed in lung tissues affected by BPD. In vitro, YAP and Wnt3a overexpression in BPd promoted AEcII proliferation and differentiation into AECIs by increasing the nuclear transfer of β-catenin and vice versa. The effects of a decreased Wnt3a expression in primary AECIIs in BPD were compensated by YAP overexpression, as were the effects of Wnt3a knockdown in primary AECIIs. On the whole, the findings of the present study demonstrate that YAP and Wnt3a independently promote AECII proliferation and differentiation in experimental BPd by increasing the nuclear β-catenin levels. Therefore, Wnt3a or YAP may be candidate regulatory targets for improving the outcomes of BPD.