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Transcriptional Changes in Radiation-Induced Lung Injury: A Comparative Analysis of Two Radiation Doses for Preclinical Research

Authors
 Mohamed El-Agamy Farh  ;  Hyun-Jin Kim  ;  Sang-Yeon Kim  ;  Jae-Hee Lee  ;  Hajeong Lee  ;  Ronglan Cui  ;  Soorim Han  ;  Dong Wook Kim  ;  Sunjoo Park  ;  Yoon-Jin Lee  ;  Yun-Sil Lee  ;  Insuk Sohn  ;  Jaeho Cho 
Citation
 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, Vol.25(7) : 3766, 2024-04 
Journal Title
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
ISSN
 1661-6596 
Issue Date
2024-04
MeSH
Animals ; Inflammation ; Interferon-gamma / genetics ; Lung ; Lung Injury* / genetics ; Pulmonary Fibrosis* / genetics ; Radiation Dosage ; Radiation Injuries*
Keywords
65 Gy and 75 Gy ; RNA sequencing ; histopathological analysis ; inflammation and fibrosis stages ; micro-computed tomography ; radiation-induced lung injury ; stereotactic body radiation therapy
Abstract
In a recent stereotactic body radiation therapy animal model, radiation pneumonitis and radiation pulmonary fibrosis were observed at around 2 and 6 weeks, respectively. However, the molecular signature of this model remains unclear. This study aimed to examine the molecular characteristics at these two stages using RNA-seq analysis. Transcriptomic profiling revealed distinct transcriptional patterns for each stage. Inflammatory response and immune cell activation were involved in both stages. Cell cycle processes and response to type II interferons were observed during the inflammation stage. Extracellular matrix organization and immunoglobulin production were noted during the fibrosis stage. To investigate the impact of a 10 Gy difference on fibrosis progression, doses of 45, 55, and 65 Gy were tested. A dose of 65 Gy was selected and compared with 75 Gy. The 65 Gy dose induced inflammation and fibrosis as well as the 75 Gy dose, but with reduced lung damage, fewer inflammatory cells, and decreased collagen deposition, particularly during the inflammation stage. Transcriptomic analysis revealed significant overlap, but differences were observed and clarified in Gene Ontology and KEGG pathway analysis, potentially influenced by changes in interferon-gamma-mediated lipid metabolism. This suggests the suitability of 65 Gy for future preclinical basic and pharmaceutical research connected with radiation-induced lung injury.
Files in This Item:
T202402491.pdf Download
DOI
10.3390/ijms25073766
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Radiation Oncology (방사선종양학교실) > 1. Journal Papers
Yonsei Authors
Kim, Dong Wook(김동욱) ORCID logo https://orcid.org/0000-0002-5819-9783
Cho, Jae Ho(조재호) ORCID logo https://orcid.org/0000-0001-9966-5157
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/199163
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