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LXA(4)-FPR2 signaling regulates radiation-induced pulmonary fibrosis via crosstalk with TGF-beta/Smad signaling
- Title
- LXA(4)-FPR2 signaling regulates radiation-induced pulmonary fibrosis via crosstalk with TGF-beta/Smad signaling
- Authors
- Kim, Hyunjung; Park, Sung-Hyo; Han, Song Yee; Lee, Yun-Sil; Cho, Jaeho; Kim, Jin-Mo
- Ewha Authors
- 이윤실
- SCOPUS Author ID
- 이윤실
- Issue Date
- 2020
- Journal Title
- CELL DEATH & DISEASE
- ISSN
- 2041-4889
- Citation
- CELL DEATH & DISEASE vol. 11, no. 8
- Publisher
- SPRINGERNATURE
- Indexed
- SCIE; SCOPUS
- Document Type
- Article
- Abstract
- Radiation therapy is an important modality in the treatment of lung cancer, but it can lead to radiation pneumonitis, and eventually radiation fibrosis. To date, only few available drugs can effectively manage radiation-induced pulmonary fibrosis. Lipoxins are endogenous molecules exhibit anti-inflammatory and pro-resolving effects. These molecules play a vital role in reducing excessive tissue injury and chronic inflammation; however, their effects on radiation-induced lung injury (RILI) are unknown. In this study, we investigated the effects of lipoxin A(4) (LXA(4)) on RILI using our specialized small-animal model of RILI following focal-ablative lung irradiation (IR). LXA(4) significantly inhibited immune-cell recruitment and reduced IR-induced expression of pro-inflammatory cytokines and fibrotic proteins in the lung lesion sites. In addition, micro-CT revealed that LXA(4) reduced IR-induced increases in lung consolidation volume. The flexiVent(TM) assays showed that LXA4 significantly reversed IR-induced lung function damage. Moreover, LXA4 downregulated the activities of NF-kappa B and the Smad-binding element promoters. The expression of FPR2, an LXA(4) receptor, increased during the development of IR-induced pulmonary fibrosis, whereas silencing of endogenous LXA(4) using an antagonist (WRW4) or FPR2 siRNA resulted in impaired development of pulmonary fibrosis in response to IR. Collectively, these data suggest that LXA(4) could serve as a potent therapeutic agent for alleviating RILI.
- DOI
- 10.1038/s41419-020-02846-7
- Appears in Collections:
- 약학대학 > 약학과 > Journal papers
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