Haplodeletion of Follistatin-like 1 Attenuates Radiation-induced Pulmonary Fibrosis in Mice.

PURPOSE: Radiation-induced pulmonary fibrosis (RIPF) is a severe and life-threatening complication of radiotherapy in thoracic cancer patients; 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.

EXPERIMENTAL DESIGN: Protein and mRNA levels of Fstl1 in lung tissues from symptomatic RIPF patients, Rhesus macaques and mice were assessed. Then, fibrotic and inflammatory responses to radiation-induced lung injury as well as 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 radiotherapy of thoracic cancer patients.