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Focal exposure of limited lung volumes to high-dose irradiation down-regulated organ development-related functions and up-regulated the immune response in mouse pulmonary tissues

Title
Focal exposure of limited lung volumes to high-dose irradiation down-regulated organ development-related functions and up-regulated the immune response in mouse pulmonary tissues
Authors
Kim B.-Y.Jin H.Lee Y.-J.Kang G.-Y.Cho J.Lee Y.-S.
Ewha Authors
이윤실
SCOPUS Author ID
이윤실scopus
Issue Date
2016
Journal Title
BMC Genetics
ISSN
1471-2156JCR Link
Citation
vol. 17, no. 1
Keywords
Focal radiationImmune responseMicroarrayOrgan developmentStereotactic body radiotherapy
Publisher
BioMed Central Ltd.
Indexed
SCIE; SCOPUS WOS scopus
Abstract
Background: Despite the emergence of stereotactic body radiotherapy (SBRT) for treatment of medically inoperable early-stage non-small-cell lung cancer patients, the molecular effects of focal exposure of limited lung volumes to high-dose radiation have not been fully characterized. This study was designed to identify molecular changes induced by focal high-dose irradiation using a mouse model of SBRT. Results: Central areas of the mouse left lung were focally-irradiated (3mm in diameter) with a single high-dose of radiation (90Gy). Temporal changes in gene expression in the irradiated and non-irradiated neighboring lung regions were analyzed by microarray. For comparison, the long-term effect (12months) of 20Gy radiation on a diffuse region of lung was also measured. The majority of genes were down-regulated in the focally-irradiated lung areas at 2 to 3weeks after irradiation. This pattern of gene expression was clearly different than gene expression in the diffuse region of lungs exposed to low-dose radiation. Ontological and pathway analyses indicated these down-regulated genes were mainly associated with organ development. Although the number was small, genes that were up-regulated after focal irradiation were associated with immune-related functions. The temporal patterns of gene expression and the associated biological functions were also similar in non-irradiated neighboring lung regions, although statistical significance was greatly reduced when compared with those from focally-irradiated areas of the lung. From network analysis of temporally regulated genes, we identified inter-related modules associated with diverse functions, including organ development and the immune response, in both the focally-irradiated regions and non-irradiated neighboring lung regions. Conclusions: Focal exposure of lung tissue to high-dose radiation induced expression of genes associated with organ development and the immune response. This pattern of gene expression was also observed in non-irradiated neighboring areas of lung tissue, indicating a global lung response to focal high-dose irradiation. © 2016 Kim et al.
DOI
10.1186/s12863-016-0338-9
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약학대학 > 약학과 > Journal papers
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