Advanced

Gpr116 Receptor Regulates Distinctive Functions in Pneumocytes and Vascular Endothelium.

Niaudet, Colin; Hofmann, Jennifer J; Mäe, Maarja A; Jung, Bongnam; Gaengel, Konstantin; Vanlandewijck, Michael; Ekvärn, Elisabet; Salvado, M Dolores; Mehlem, Annika and Al Sayegh, Sahar, et al. (2015) In PLoS ONE 10(9).
Abstract
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... (More)
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. (Less)
Please use this url to cite or link to this publication:
author
, et al. (More)
(Less)
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
PLoS ONE
volume
10
issue
9
publisher
Public Library of Science
external identifiers
  • pmid:26394398
  • wos:000361792100023
  • scopus:84947736706
ISSN
1932-6203
DOI
10.1371/journal.pone.0137949
language
English
LU publication?
yes
id
6922005e-0e7d-49a6-9122-740f5f142960 (old id 8035316)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/26394398?dopt=Abstract
date added to LUP
2015-10-03 17:12:47
date last changed
2017-09-17 05:57:31
@article{6922005e-0e7d-49a6-9122-740f5f142960,
  abstract     = {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.},
  articleno    = {e0137949},
  author       = {Niaudet, Colin and Hofmann, Jennifer J and Mäe, Maarja A and Jung, Bongnam and Gaengel, Konstantin and Vanlandewijck, Michael and Ekvärn, Elisabet and Salvado, M Dolores and Mehlem, Annika and Al Sayegh, Sahar and He, Liqun and Lebouvier, Thibaud and Castro-Freire, Marco and Katayama, Kan and Hultenby, Kjell and Moessinger, Christine and Tannenberg, Philip and Cunha, Sara and Pietras, Kristian and Laviña, Bàrbara and Hong, JongWook and Berg, Tove and Betsholtz, Christer},
  issn         = {1932-6203},
  language     = {eng},
  number       = {9},
  publisher    = {Public Library of Science},
  series       = {PLoS ONE},
  title        = {Gpr116 Receptor Regulates Distinctive Functions in Pneumocytes and Vascular Endothelium.},
  url          = {http://dx.doi.org/10.1371/journal.pone.0137949},
  volume       = {10},
  year         = {2015},
}