Zhongjie Chen1, Yinshan Fang2, Si Zhang2, Lian Li2, Li Wang2, Aixu Zhang3, Zhiyong Yuan3, Ping Wang3, Honggang Zhou4, Wanchang Cui5, Thomas J MacVittie5, Wen Ning2. 1. Department of Radiation Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin's Clinical Research Center for Cancer, Tianjin, China. Electronic address: zchen01@tmu.edu.cn. 2. State Key Laboratory of Medical Chemical Biology, College of Life Sciences, Nankai University, Tianjin, China. 3. Department of Radiation Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin's Clinical Research Center for Cancer, Tianjin, China. 4. College of Pharmacy, Nankai University, Tianjin, China. 5. Department of Radiation Oncology, University of Maryland, School of Medicine, Baltimore, Maryland.
Abstract
PURPOSE: 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.
PURPOSE: 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.
Authors: Nicholas A Maksimowski; Xuewen Song; Eun Hui Bae; Heather Reich; Rohan John; York Pei; James W Scholey Journal: Int J Mol Sci Date: 2021-09-01 Impact factor: 5.923