TY - JOUR
T1 - Transcriptional Changes in Radiation-Induced Lung Injury
T2 - A Comparative Analysis of Two Radiation Doses for Preclinical Research
AU - Farh, Mohamed El Agamy
AU - Kim, Hyun Jin
AU - Kim, Sang Yeon
AU - Lee, Jae Hee
AU - Lee, Hajeong
AU - Cui, Ronglan
AU - Han, Soorim
AU - Kim, Dong Wook
AU - Park, Sunjoo
AU - Lee, Yoon Jin
AU - Lee, Yun Sil
AU - Sohn, Insuk
AU - Cho, Jaeho
N1 - Publisher Copyright:
© 2024 by the authors.
PY - 2024/4
Y1 - 2024/4
N2 - 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.
AB - 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.
KW - 65 Gy and 75 Gy
KW - RNA sequencing
KW - histopathological analysis
KW - inflammation and fibrosis stages
KW - micro-computed tomography
KW - radiation-induced lung injury
KW - stereotactic body radiation therapy
UR - http://www.scopus.com/inward/record.url?scp=85190388506&partnerID=8YFLogxK
U2 - 10.3390/ijms25073766
DO - 10.3390/ijms25073766
M3 - Article
C2 - 38612576
AN - SCOPUS:85190388506
SN - 1661-6596
VL - 25
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
IS - 7
M1 - 3766
ER -