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ORIGINAL RESEARCH article

Front. Oncol.
Sec. Radiation Oncology
Volume 14 - 2024 | doi: 10.3389/fonc.2024.1406759

Spleen Tyrosine Kinase Inhibition Mitigates Radiation-induced Lung Injury Through Anti-inflammatory Effects and Downregulation of p38 MAPK and p53

Provisionally accepted
Guoxing Zhang Guoxing Zhang 1Ni Sun Ni Sun 1Xiaohua Li Xiaohua Li 2*
  • 1 Department of Intensive Care Unit, Jilin Province Tumor Hospital, Changchun, Jilin Province, China
  • 2 Department of Infectious Diseases, First Affiliated Hospital of Jilin University, Changchun, China

The final, formatted version of the article will be published soon.

    Background: To explore new modulatory intervention targets for radiation-induced lung injury, bioinformatics analysis technology was used to search for the core driving genes in the pathogenesis of radiation pneumonitis, and the results were verified by a radiation-induced murine lung injury model to find possible new targets for the treatment of radiation lung injury.Method: Gene Expression Omnibus Database was used to identify Differentially expressed genes in radiation pneumonitis. DAVID database was used for gene ontology (GO) and Kyoto Encyclopedia of genes and genome (KEGG) enrichment analysis.Gene Set Enrichment Analysis was used to analyze abnormal expressions. Proteinprotein interaction networks were constructed using STRING and Cytoscape. Discovery Studio 4.5 software was used to find the preferred inhibitor of the specific gene. A radiation-induced lung injury model was induced in female C57BL/6N mice.The specific inhibitors were administered by intraperitoneal injection 24 hours before and for 7 consecutive days after radiation. Lungs were harvested for further analysis 14 days and 10 weeks postirradiation.We screened Syk as one of the most important driver genes of radiation pneumonitis by bioinformatics analysis, and screened the preferred Syk inhibitor fostamatinib from the drug database. Syk was highly expressed in irradiated lung tissue, fostamatinib inhibited the level of Syk expression. Syk inhibitor significantly alleviated the radiation-induced lung injury, and downregulated the increased expression of p38 MAPK, p53, IL-1β and IL-6 in lung tissue at 2 weeks after radiation. The level of TGF-β, COL1A1, α-SMA level, and degree of pulmonary fibrosis at 10 weeks after radiation was also decreased by Syk inhibitor.Syk inhibitor may have a potential to be used as a targeted drug to mitigate radiation pneumonitis and inhibit the radiation-induced pulmonary fibrosis.

    Keywords: bioinformatics, Radiation Pneumonitis, Syk, p38 MAPK, p53

    Received: 25 Mar 2024; Accepted: 11 Oct 2024.

    Copyright: © 2024 Zhang, Sun and Li. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Xiaohua Li, Department of Infectious Diseases, First Affiliated Hospital of Jilin University, Changchun, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.