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

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

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

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.

Original languageEnglish
Article number3766
JournalInternational Journal of Molecular Sciences
Volume25
Issue number7
DOIs
StatePublished - Apr 2024

Bibliographical note

Publisher Copyright:
© 2024 by the authors.

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

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