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Open AccessArticle

Metabolomic Analysis Reveals Unique Biochemical Signatures Associated with Protection from Radiation Induced Lung Injury by Lack of cd47 Receptor Gene Expression

1
Department of Cancer Biology, Wake Forest School of Medicine Comprehensive Cancer Center, Winston-Salem, NC 27101, USA
2
Wake Forest School of Medicine Comprehensive Cancer Center, Winston-Salem, NC 27101, USA
3
Department of Surgery, Wake Forest School of Medicine Comprehensive Cancer Center, Winston-Salem, NC 27101, USA
4
Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
5
Department of Radiation Oncology, Wake Forest School of Medicine Comprehensive Cancer Center, Winston-Salem, NC 27101, USA
*
Author to whom correspondence should be addressed.
Metabolites 2019, 9(10), 218; https://doi.org/10.3390/metabo9100218
Received: 30 August 2019 / Revised: 20 September 2019 / Accepted: 30 September 2019 / Published: 8 October 2019
(This article belongs to the Special Issue Metabolomics in the Study of Disease)
The goal of this study was to interrogate biochemical profiles manifested in mouse lung tissue originating from wild type (WT) and cd47 null mice with the aim of revealing the in vivo role of CD47 in the metabolic response to ionizing radiation, especially changes related to the known association of CD47 deficiency with increased tissue viability and survival. For this objective, we performed global metabolomic analysis in mouse lung tissue collected from (C57Bl/6 background) WT and cd47 null mice with and without exposure to 7.6 Gy whole body radiation. Principal component analysis and hierarchical clustering revealed a consistent separation between genotypes following radiation exposure. Random forest analysis also revealed a unique biochemical signature in WT and cd47 null mice following treatment. Our data show that cd47 null irradiated lung tissue activates a unique set of metabolic pathways that facilitate the handling of reactive oxygen species, lipid metabolism, nucleotide metabolism and nutrient metabolites which may be regulated by microbial processing. Given that cd47 has pleiotropic effects on responses to ionizing radiation, we not only propose this receptor as a therapeutic target but postulate that the biomarkers regulated in this study associated with radioprotection are potential mitigators of radiation-associated pathologies, including the onset of pulmonary disease. View Full-Text
Keywords: ionizing radiation; radiation-induced lung injury; CD47; thrombospondin-1; redox; amino acid; fatty acid; lipid; xenobiotics ionizing radiation; radiation-induced lung injury; CD47; thrombospondin-1; redox; amino acid; fatty acid; lipid; xenobiotics
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Stirling, E.R.; Cook, K.L.; Roberts, D.D.; Soto-Pantoja, D.R. Metabolomic Analysis Reveals Unique Biochemical Signatures Associated with Protection from Radiation Induced Lung Injury by Lack of cd47 Receptor Gene Expression. Metabolites 2019, 9, 218.

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