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Angiogenic signaling in the lungs of a metabolically suppressed hibernating mammal (Ictidomys tridecemlineatus)
- Source :
- PeerJ, Vol 7, p e8116 (2019), PeerJ
- Publication Year :
- 2019
- Publisher :
- PeerJ Inc., 2019.
-
Abstract
- To conserve energy in times of limited resource availability, particularly during cold winters, hibernators suppress even the most basic of physiologic processes. Breathing rates decrease from 40 breaths/minute to less than 1 breath/min as they decrease body temperature from 37 °C to ambient. Nevertheless, after months of hibernation, these incredible mammals emerge from torpor unscathed. This study was conducted to better understand the protective and possibly anti-inflammatory adaptations that hibernator lungs may use to prevent damage associated with entering and emerging from natural torpor. We postulated that the differential protein expression of soluble protein receptors (decoy receptors that sequester soluble ligands to inhibit signal transduction) would help identify inhibited inflammatory signaling pathways in metabolically suppressed lungs. Instead, the only two soluble receptors that responded to torpor were sVEGFR1 and sVEGFR2, two receptors whose full-length forms are bound by VEGF-A to regulate endothelial cell function and angiogenesis. Decreased sVEGFR1/2 correlated with increased total VEGFR2 protein levels. Maintained or increased levels of key γ-secretase subunits suggested that decreased sVEGFR1/2 protein levels were not due to decreased levels of intramembrane cleavage complex subunits. VEGF-A protein levels did not change, suggesting that hibernators may regulate VEGFR1/2 signaling at the level of the receptor instead of increasing relative ligand abundance. A panel of angiogenic factors used to identify biomarkers of angiogenesis showed a decrease in FGF-1 and an increase in BMP-9. Torpid lungs may use VEGF and BMP-9 signaling to balance angiogenesis and vascular stability, possibly through the activation of SMAD signaling for adaptive tissue remodeling.
- Subjects :
- Hibernation
Angiogenesis
lcsh:Medicine
SMAD
Biochemistry
General Biochemistry, Genetics and Molecular Biology
Tissue remodeling
03 medical and health sciences
0302 clinical medicine
Decoy receptors
Receptor
BMP-9
Molecular Biology
Lung
030304 developmental biology
0303 health sciences
Chemistry
General Neuroscience
Soluble receptor
lcsh:R
Metabolic suppression
General Medicine
Torpor
VEGF
Cell biology
Endothelial stem cell
Ground squirrel
030220 oncology & carcinogenesis
Signal transduction
General Agricultural and Biological Sciences
Zoology
Subjects
Details
- Language :
- English
- ISSN :
- 21678359
- Volume :
- 7
- Database :
- OpenAIRE
- Journal :
- PeerJ
- Accession number :
- edsair.doi.dedup.....c691377be5064f6e55cdb47fd687085f