Endothelial YAP1 in Regenerative Lung Growth through the Angiopoietin-Tie2 Pathway. Am J Respir Cell Mol Biol 2019 Jan;60(1):117-127
Date
08/30/2018Pubmed ID
30156429Pubmed Central ID
PMC6348720DOI
10.1165/rcmb.2018-0105OCScopus ID
2-s2.0-85059234576 (requires institutional sign-in at Scopus site) 31 CitationsAbstract
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.
Author List
Mammoto T, Muyleart M, Mammoto AAuthors
Akiko Mammoto MD, PhD Associate Professor in the Pediatrics department at Medical College of WisconsinTadanori Mammoto MD, PhD Associate Professor in the Pediatrics department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
Adaptor Proteins, Signal TransducingAngiopoietins
Animals
Cell Cycle Proteins
Cell Proliferation
Humans
Lung
Mice
Mice, Knockout
Neovascularization, Physiologic
Organogenesis
Phosphoproteins
Pneumonectomy
Receptor, TIE-2
Regeneration
Signal Transduction
Transcription Factors
