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  3. The role of cGAS-STING pathway in the development of radiation-induced lung injury

The role of cGAS-STING pathway in the development of radiation-induced lung injury

  • J Cancer Res Clin Oncol. 2025 Jan 25;151(2):48. doi: 10.1007/s00432-025-06088-y.
Xinyao Zhao # 1,  Lehui Du # 2,  Na Ma # 2,  Xin Tan 2,  Xiao Lei 2,  Pei Zhang 2,  Baolin Qu 3
Affiliations

Affiliations

  • 1 Department of Radiation Oncology, Shijingshan Teaching Hospital of Capital Medical University, Shijingshan Hospital, Beijing, China.
  • 2 Department of Radiation Oncology, The First Medical Center of Chinese PLA General Hospital, Beijing, China.
  • 3 Department of Radiation Oncology, The First Medical Center of Chinese PLA General Hospital, Beijing, China. qubl6212@sina.com.
  • # Contributed equally.
PMID: 39856464 DOI: 10.1007/s00432-025-06088-y
Abstract

Background and purpose: Radiation-induced lung injury (RILI) limits the efficacy of thoracic radiotherapy. However, the underlying mechanism of RILI remains unclear. cGAS-STING pathway is reported to be involved in the recognization of cytosolic dsDNA and various inflammatory diseases. This study aimed to investigate the role of cGAS-STING pathway in the development of RILI.

Materials and methods: A pre-clinical mouse model of RILI was established by whole thorax irradiation and confirmed using H&E and Masson's trichrome staining. STING agonist (DMXAA) and antagonist(C-176) were administrated to modulate cGAS-STING pathway in vivo. Western blot and ELISA were used to determine the expression levels of different proteins.

Results: Quantitation analysis showed dsDNA accumulation in lung tissue and western blot showed the up-regulation of cGAS and STING protein level post-irradiation, indicating pathway activation. Histological evaluation showed that C-176 administration ameliorated radiation-induced pulmonary inflammation and fibrosis, while DMXAA exhibited contrary effects. In further in vitro study, the release of dsDNA induced by radiation led to the activation of cGAS-STING pathway in RAW 264.7 cells, resulting in the polarization into M1 phenotype and pro-inflammatory production.

Conclusion: In summary, our data demonstrated a link between cGAS-STING pathway and the development of RILI, indicating its potential application in clinic.

Keywords

M1 polarization; Macrophage; Radiation-induced lung injury; cGAS-STING signaling pathway.

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