Fig. 2

Diverse roles of the Hippo pathway in epithelial cells and progenitor cells. a The Hippo pathway is involved in fundamental cellular functions, such as proliferation, differentiation, regeneration, cellular senescence, and regulated cell death. The appropriate regulation of the Hippo pathway in lung epithelial cells is essential for the maintenance of tissue homeostasis. Observed in IPF lungs are dysfunctional epithelial cells. In particular, epithelial cells with impaired differentiation, leading to features of both basal and mesenchymal cells, have been revealed as pathogenic epithelial populations. Furthermore, increased senescent cells and cells undergoing cell death due to repetitive cellular stresses play an important role in the progression of IPF. b Alveoli are lined by AT1 and AT2 cells. In acute lung injury, NF-κB is upregulated in the AT2 cells, and inflammation occurs. In response to the damage, YAP is activated in AT2 cells and promotes their proliferation. Furthermore, YAP induces IκBα expression in AT2 cells for resolution of the inflammation. In addition, upregulated YAP causes AT2 cells to differentiate into AT1 cells to promote tissue repair. c In the airway, basal progenitor cells and secretory cells comprise the pseudostratified epithelial architecture. Both types of cells transit reciprocally between each other, depending on YAP expression. When YAP is downregulated in basal progenitor cells, which then differentiate into secretory cells. In contrast, increased YAP expression in the differentiated cells causes them to dedifferentiate and acquire stemness. On the other hand, YAP overexpression in basal progenitor cells leads to their proliferation and stratification. With these findings, YAP can be considered a key factor for regulating tissue regeneration after injury by balancing quiescent and proliferative states