Haplodeletion of Follistatin-Like 1 Attenuates Radiation-Induced Pulmonary Fibrosis in Mice
JournalInternational Journal of Radiation Oncology Biology Physics
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AbstractPurpose: Radiation-induced pulmonary fibrosis (RIPF) is a severe and life-threatening complication of radiation therapy in patients with thoracic cancer; however, the exact molecular mechanisms remain unknown, and there is no effective treatment method in clinic. Here, we assessed the role of follistatin-like 1 (Fstl1) in RIPF. Methods and Materials: Protein and messenger RNA levels of Fstl1 in lung tissues from symptomatic RIPF patients, Rhesus macaques, and mice were assessed. Fibrotic and inflammatory responses to radiation-induced lung injury and accumulation of myofibroblasts in Fstl1 haplodeficient (Fstl1+/–) mice were determined. Finally, radiation-induced differentiation and activation of fibroblasts in primary Fstl1+/– lung fibroblasts were evaluated. Results: FSTL1 amounts were significantly increased in serum and/or radiation-injured lung specimens from symptomatic RIPF patients, Rhesus macaques, and mice. Haplodeletion of Fstl1 in Fstl1+/– mice was protective against x-ray–induced lung injury in mice in vivo, as well as myofibroblast activation in vitro. Conclusions: These findings suggest that Fstl1 plays an important role in lung fibrosis and may offer a potential approach to attenuate RIPF in radiation therapy of patients with thoracic cancer.
Identifier to cite or link to this itemhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85057863487&doi=10.1016%2fj.ijrobp.2018.08.035&partnerID=40&md5=8ab3b392cea8b4e6c41d0cc96759751b; http://hdl.handle.net/10713/10650
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