Format

Send to

Choose Destination
Am J Respir Cell Mol Biol. 2019 Jan;60(1):117-127. doi: 10.1165/rcmb.2018-0105OC.

Endothelial YAP1 in Regenerative Lung Growth through the Angiopoietin-Tie2 Pathway.

Author information

1
1 Department of Radiology and.
2
2 Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin.

Abstract

Angiogenesis, the formation of new blood capillaries, plays a key role in organ development and regeneration. Inhibition of lung angiogenesis through the blockade of angiogenic signaling pathways impairs compensatory and regenerative lung growth after unilateral pneumonectomy (PNX). The Hippo signaling transducer, Yes-associated protein (YAP) 1 binds to TEA domain transcription factor (TEAD) and controls organ size and regeneration. However, the role of endothelial YAP1 in lung vascular and alveolar morphogenesis remains unclear. In this report, we demonstrate that knockdown of YAP1 in endothelial cells (ECs) decreases angiogenic factor receptor Tie2 expression, and inhibits EC sprouting and epithelial cell budding in vitro and vascular and alveolar morphogenesis in the gel implanted on the mouse lung. The expression levels of YAP1, TEAD1, and Tie2 increase in ECs isolated from the remaining mouse lungs after unilateral PNX and vascular formation is stimulated in the post-PNX mouse lungs. Knockdown of endothelial YAP1 inhibits compensatory lung growth and vascular and alveolar morphogenesis after unilateral PNX. These findings suggest that endothelial YAP1 is required for lung vascular and alveolar regeneration and modulation of YAP1 in ECs may be novel interventions for the improvement of lung regeneration.

KEYWORDS:

TEAD1; Tie2; YAP1; angiogenesis; lung regeneration

PMID:
30156429
PMCID:
PMC6348720
[Available on 2020-01-01]
DOI:
10.1165/rcmb.2018-0105OC
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Atypon
Loading ...
Support Center