Gpr116 Receptor Regulates Distinctive Functions in Pneumocytes and Vascular Endothelium
Colin Niaudet1, Jennifer J Hofmann2, Maarja A Mäe1
1Department of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden.
Plos One
|September 23, 2015
Summary
The adhesion receptor Gpr116 regulates lung surfactant homeostasis, preventing emphysema-like pathology. Loss of Gpr116 also causes cerebral vascular leakage, highlighting its crucial role in both pulmonary and central nervous system vasculature.
Area of Science:
- Molecular Biology
- Physiology
- Pathology
Background:
- The adhesion receptor Gpr116 (ADGRF5) is expressed in vascular endothelium and lung epithelium.
- Its precise physiological functions remained largely unknown until recently.
Purpose of the Study:
- To investigate the physiological role of Gpr116 using a novel constitutive knockout mouse model.
- To elucidate Gpr116's function in pulmonary and cerebrovascular systems.
Main Methods:
- Generation of a constitutive Gpr116 knockout mouse model with a large genetic deletion.
- Analysis of pulmonary surfactant homeostasis, lung pathology, and cerebrovascular leakage.
- Endothelial-specific deletion of Gpr116 and assessment in oxygen-induced retinopathy model.
Main Results:
- Gpr116 deficiency leads to surfactant accumulation, macrophage infiltration, and emphysema-like lung pathology.
- Loss of Gpr116 causes cerebral vascular leakage starting at 1.5 months of age.
- Endothelial Gpr116 deletion exacerbates brain vascular leakage, while its absence attenuates retinal vascular response.
Conclusions:
- Gpr116 is essential for maintaining pulmonary surfactant homeostasis.
- Gpr116 plays a significant, previously unrecognized role in regulating central nervous system vasculature.
- Gpr116 modulates endothelial properties in both pulmonary and vascular systems.
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