Pulmonary pericytes regulate lung morphogenesis

Katsuhiro Kato (), Rodrigo Diéguez-Hurtado, Do Young Park, Seon Pyo Hong, Sakiko Kato-Azuma, Susanne Adams, Martin Stehling, Britta Trappmann, Jeffrey L. Wrana, Gou Young Koh and Ralf H. Adams ()
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Katsuhiro Kato: Max Planck Institute for Molecular Biomedicine, and University of Münster, Faculty of Medicine
Rodrigo Diéguez-Hurtado: Max Planck Institute for Molecular Biomedicine, and University of Münster, Faculty of Medicine
Do Young Park: Institute of Basic Science (IBS)
Seon Pyo Hong: Institute of Basic Science (IBS)
Sakiko Kato-Azuma: Max Planck Institute for Molecular Biomedicine, and University of Münster, Faculty of Medicine
Susanne Adams: Max Planck Institute for Molecular Biomedicine, and University of Münster, Faculty of Medicine
Martin Stehling: Max Planck Institute for Molecular Biomedicine
Britta Trappmann: Max Planck Institute for Molecular Biomedicine
Jeffrey L. Wrana: Mount Sinai Hospital
Gou Young Koh: Institute of Basic Science (IBS)
Ralf H. Adams: Max Planck Institute for Molecular Biomedicine, and University of Münster, Faculty of Medicine

Nature Communications, 2018, vol. 9, issue 1, 1-14

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-018-04913-2

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