1. Inhibition of TGFβ1 activation prevents radiation‐induced lung fibrosis
- Author
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Minxiao Yi, Ye Yuan, Li Ma, Long Li, Wan Qin, Bili Wu, Bolong Zheng, Xin Liao, Guangyuan Hu, and Bo Liu
- Subjects
cilengitide ,radiation‐induced pulmonary fibrosis ,transforming growth factor beta 1 ,αv integrin ,Medicine (General) ,R5-920 - Abstract
Abstract Background Radiotherapy is the main treatment modality for thoracic tumours, but it may induce pulmonary fibrosis. Currently, the pathogenesis of radiation‐induced pulmonary fibrosis (RIPF) is unclear, and effective treatments are lacking. Transforming growth factor beta 1 (TGFβ1) plays a central role in RIPF. We found that activated TGFβ1 had better performance for radiation pneumonitis (RP) risk prediction by detecting activated and total TGFβ1 levels in patient serum. αv integrin plays key roles in TGFβ1 activation, but the role of αv integrin‐mediated TGFβ1 activation in RIPF is unclear. Here, we investigated the role of αv integrin‐mediated TGFβ1 activation in RIPF and the application of the integrin antagonist cilengitide to prevent RIPF. Methods ItgavloxP/loxP;Pdgfrb‐Cre mice were generated by conditionally knocking out Itgav in myofibroblasts, and wild‐type mice were treated with cilengitide or placebo. All mice received 16 Gy of radiation or underwent a sham radiation procedure. Lung fibrosis was measured by a modified Ashcroft score and microcomputed tomography (CT). An enzyme‐linked immunosorbent assay (ELISA) was used to measure the serum TGFβ1 concentration, and total Smad2/3 and p‐Smad2/3 levels were determined via Western blotting. Results Conditional Itgav knockout significantly attenuated RIPF (p
- Published
- 2024
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