Hippo-YAP/TAZ Signaling in the Respiratory System.

Abstract

The Hippo signaling pathway and its effectors Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) have emerged as central regulators of respiratory biology, playing essential functions in the development, homeostasis, and regeneration of the lung and trachea. Here, we review the spatiotemporal control of core pathway components in murine and human lungs, highlighting how YAP and TAZ integrate mechanical and molecular cues to govern epithelial patterning, mesenchymal function, vascular integrity, and stem cell behavior. We provide an overview of the mechanisms by which Hippo-YAP/TAZ signaling directs lung injury repair, while also exploring how its dysregulation contributes to fibrosis, vascular remodeling, and lung tumorigenesis. Finally, we discuss the importance of restoring or targeting YAP/TAZ-TEAD activity in the lung and consider the opportunities and challenges associated with pharmacologic inhibition in pulmonary disease.