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Nat Commun. 2018 Jun 22;9(1):2448. doi: 10.1038/s41467-018-04913-2.

Pulmonary pericytes regulate lung morphogenesis.

Author information

1
Department of Tissue Morphogenesis, Max Planck Institute for Molecular Biomedicine, and University of Münster, Faculty of Medicine, D-48149, Münster, Germany. katsuhiro.kato@mpi-muenster.mpg.de.
2
Department of Tissue Morphogenesis, Max Planck Institute for Molecular Biomedicine, and University of Münster, Faculty of Medicine, D-48149, Münster, Germany.
3
Center for Vascular Research, Institute of Basic Science (IBS), Daejeon, 34141, Republic of Korea.
4
Graduate School of Medical Science and Engineering, and Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 34141, Korea.
5
Electron Microscopy and Flow Cytometry Units, Max Planck Institute for Molecular Biomedicine, D-48149, Münster, Germany.
6
Bioactive Materials Laboratory, Max Planck Institute for Molecular Biomedicine, D-48149, Münster, Germany.
7
Centre for Systems Biology, Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, M5G 1X5, Canada.
8
Department of Molecular Genetics, University of Toronto, Toronto, ON, M5S 1A8, Canada.
9
Department of Tissue Morphogenesis, Max Planck Institute for Molecular Biomedicine, and University of Münster, Faculty of Medicine, D-48149, Münster, Germany. ralf.adams@mpi-muenster.mpg.de.

Abstract

Blood vessels are essential for blood circulation but also control organ growth, homeostasis, and regeneration, which has been attributed to the release of paracrine signals by endothelial cells. Endothelial tubules are associated with specialised mesenchymal cells, termed pericytes, which help to maintain vessel wall integrity. Here we identify pericytes as regulators of epithelial and endothelial morphogenesis in postnatal lung. Mice lacking expression of the Hippo pathway components YAP and TAZ in pericytes show defective alveologenesis. Mutant pericytes are present in normal numbers but display strongly reduced expression of hepatocyte growth factor leading to impaired activation of the c-Met receptor, which is expressed by alveolar epithelial cells. YAP and TAZ are also required for expression of angiopoietin-1 by pulmonary pericytes, which also controls hepatocyte growth factor expression and thereby alveologenesis in an autocrine fashion. These findings establish that pericytes have important, organ-specific signalling properties and coordinate the behavior of epithelial and vascular cells during lung morphogenesis.

PMID:
29934496
PMCID:
PMC6015030
DOI:
10.1038/s41467-018-04913-2
[Indexed for MEDLINE]
Free PMC Article

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