Haplodeletion of Follistatin-Like 1 Attenuates Radiation-Induced Pulmonary Fibrosis in Mice
JournalInternational Journal of Radiation Oncology Biology Physics
MetadataShow full item record
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
- Follistatin-Like 1 Promotes Bleomycin-Induced Pulmonary Fibrosis through the Transforming Growth Factor Beta 1/Mitogen-Activated Protein Kinase Signaling Pathway.
- Authors: Jin YK, Li XH, Wang W, Liu J, Zhang W, Fang YS, Zhang ZF, Dai HP, Ning W, Wang C
- Issue date: 2018 Aug 20
- Blocking follistatin-like 1 attenuates bleomycin-induced pulmonary fibrosis in mice.
- Authors: Dong Y, Geng Y, Li L, Li X, Yan X, Fang Y, Li X, Dong S, Liu X, Li X, Yang X, Zheng X, Xie T, Liang J, Dai H, Liu X, Yin Z, Noble PW, Jiang D, Ning W
- Issue date: 2015 Feb 9
- Follistatin like-1 aggravates silica-induced mouse lung injury.
- Authors: Fang Y, Zhang S, Li X, Jiang F, Ye Q, Ning W
- Issue date: 2017 Mar 24
- Follistatin like-1 (Fstl1) is required for the normal formation of lung airway and vascular smooth muscle at birth.
- Authors: Liu X, Liu Y, Li X, Zhao J, Geng Y, Ning W
- Issue date: 2017
- Muscle-derived follistatin-like 1 functions to reduce neointimal formation after vascular injury.
- Authors: Miyabe M, Ohashi K, Shibata R, Uemura Y, Ogura Y, Yuasa D, Kambara T, Kataoka Y, Yamamoto T, Matsuo K, Joki Y, Enomoto T, Hayakawa S, Hiramatsu-Ito M, Ito M, Van Den Hoff MJ, Walsh K, Murohara T, Ouchi N
- Issue date: 2014 Jul 1