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

Author:

Farh Mohamed El-Agamy12,Kim Hyun-Jin1ORCID,Kim Sang-Yeon1ORCID,Lee Jae-Hee1,Lee Hajeong1,Cui Ronglan1,Han Soorim1,Kim Dong Wook1ORCID,Park Sunjoo1,Lee Yoon-Jin3,Lee Yun-Sil4ORCID,Sohn Insuk2,Cho Jaeho1ORCID

Affiliation:

1. Department of Radiation Oncology, Yonsei University College of Medicine, Seoul 03722, Republic of Korea

2. Drug Development Team, ARONTIER, Co., Ltd., Seoul 06735, Republic of Korea

3. Korea Institute of Radiological and Medical Science, Seoul 01812, Republic of Korea

4. Graduate School of Pharmaceutical Science, Ewha Womans University, Seoul 03760, Republic of Korea

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.

Funder

National Research Foundation of Korea

Publisher

MDPI AG

Cited by 1 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

1. Evidence of alveolar macrophage metabolic shift following SBRT-induced lung fibrosis in mice;International Journal of Radiation Oncology*Biology*Physics;2024-09

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