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Gpr116 Receptor Regulates Distinctive Functions in Pneumocytes and Vascular Endothelium.

Author:
  • Colin Niaudet
  • Jennifer J Hofmann
  • Maarja A Mäe
  • Bongnam Jung
  • Konstantin Gaengel
  • Michael Vanlandewijck
  • Elisabet Ekvärn
  • M Dolores Salvado
  • Annika Mehlem
  • Sahar Al Sayegh
  • Liqun He
  • Thibaud Lebouvier
  • Marco Castro-Freire
  • Kan Katayama
  • Kjell Hultenby
  • Christine Moessinger
  • Philip Tannenberg
  • Sara Cunha
  • Kristian Pietras
  • Bàrbara Laviña
  • JongWook Hong
  • Tove Berg
  • Christer Betsholtz
Publishing year: 2015
Language: English
Publication/Series: PLoS ONE
Volume: 10
Issue: 9
Document type: Journal article
Publisher: Public Library of Science

Abstract english

Despite its known expression in both the vascular endothelium and the lung epithelium, until recently the physiological role of the adhesion receptor Gpr116/ADGRF5 has remained elusive. We generated a new mouse model of constitutive Gpr116 inactivation, with a large genetic deletion encompassing exon 4 to exon 21 of the Gpr116 gene. This model allowed us to confirm recent results defining Gpr116 as necessary regulator of surfactant homeostasis. The loss of Gpr116 provokes an early accumulation of surfactant in the lungs, followed by a massive infiltration of macrophages, and eventually progresses into an emphysema-like pathology. Further analysis of this knockout model revealed cerebral vascular leakage, beginning at around 1.5 months of age. Additionally, endothelial-specific deletion of Gpr116 resulted in a significant increase of the brain vascular leakage. Mice devoid of Gpr116 developed an anatomically normal and largely functional vascular network, surprisingly exhibited an attenuated pathological retinal vascular response in a model of oxygen-induced retinopathy. These data suggest that Gpr116 modulates endothelial properties, a previously unappreciated function despite the pan-vascular expression of this receptor. Our results support the key pulmonary function of Gpr116 and describe a new role in the central nervous system vasculature.

Keywords

  • Cell and Molecular Biology

Other

Published
  • ISSN: 1932-6203
Kristian Pietras
E-mail: kristian.pietras [at] med.lu.se

Professor

Division of Translational Cancer Research

+46 46 222 64 29

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Project manager

Experimental oncology