Abstract
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.
Highlights
Syndrome due to accidental or intentional exposure to ionizing radiation [1,2]
Our data show that cd47 null irradiated lung tissue activates a unique set of metabolic pathways that facilitate the handling of reactive oxygen species (ROS), lipid metabolism, nucleotide metabolism and nutrient metabolites which may be regulated by microbial processing
wild type (WT) and CD47 deficient Jurkat T lymphocytes cell line and observed that CD47 deficient cells and lung tissues were protected from increasing doses of ionizing radiation by the activation of autophagy [12]
Summary
Syndrome due to accidental or intentional exposure to ionizing radiation [1,2]. pulmonary tissue is exquisitely sensitive to radiation damage and is considered treatment-limiting in patients exposed to total-body irradiation (TBI) in preparation for hematopoietic stem cell transplantation [3].Metabolites 2019, 9, 218; doi:10.3390/metabo9100218 www.mdpi.com/journal/metabolitesBecause of its sensitivity to radiation, lung tissue is vulnerable to early and late effects of radiation that can impact quality of life, survival and future risk to pulmonary pathologies [4,5]. Cluster of differentiation 47 (CD47, encoded by cd in mouse) is a signaling receptor for thrombospondin-1 (TSP1) and an attractive cancer therapeutic target as blocking CD47 signaling protects normal tissue while sensitizing tumors to ionizing radiation [6,7,8]. CD47 transduces signals that alter cellular calcium, cyclic nucleotide, integrin, growth factor signaling and controls cell viability and resistances to stress [10,11]. This latter function is fundamental to understanding why targeting CD47 could provide therapeutic benefits to treat radiation-induced pathologies. In previous studies we demonstrated that the radioprotective effect of CD47 on cells and tissues, including lungs, was mediated through the activation of protective autophagy [9,12]
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