YAP1 stimulates angiogenesis and lung regeneration through the Angiopoietin‐Tie2 pathway

Abstract

Angiogenesis, the formation of new blood capillaries, plays key roles in organ development and regeneration. Inhibition of angiogenesis through the blockade of angiogenic signaling pathways impairs adult lung regeneration. Previously we have reported that Wnt co‐receptor, low‐density lipoprotein receptor‐related protein 5 controls lung vascular and alveolar regeneration. The Hippo signaling transducer, Yes‐associated protein (YAP1), cooperates with Wnt‐b‐catenin signaling and controls organ size and regeneration. Here, we have demonstrated that YAP1 knockdown decreases angiogenic factor receptor Tie2 expression and inhibits endothelial cell sprouting and lung epithelial morphogenesis in vitro. YAP1 knockdown also attenuates angiogenesis and alveolar epithelial cell recruitment into the hydrogels implanted on the mouse lungs and inhibits compensatory lung growth after unilateral pneumonectomy in adult mice. These findings suggest that YAP1 plays an important role in lung vascular and alveolar regeneration and modulation of YAP1 expression in alveolar capillary endothelial cells may be a novel strategy for lung regeneration.Support or Funding InformationBoston Children's Hospital Career Development Awards