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The Preventive Effect of Endostar on Radiation-induced Pulmonary Fibrosis

[ Vol. 24 , Issue. 5 ]


Hangjie Ying, Cheng Zhou, Qingqing Hang and Min Fang*   Pages 610 - 619 ( 10 )


<p>Background: Radiation-induced pulmonary fibrosis (RIPF) is a long-term complication of thoracic radiotherapy without effective treatment available. <p> Objective: This study aimed to establish a RIPF mouse model and explore the therapeutic effects and mechanisms of recombinant human endostatin (Endostar). <p> Methods: C57BL/6 mice received a 16-Gy dose of X-rays to the whole thorax with or without the administration of Endostar for 24 weeks. <p> Results: Radiation-induced body weight loss was partially attenuated by Endostar (P&#60;0.05). Endostar significantly reduced alveolar inflammation (P&#60;0.05) and pulmonary fibrosis (P&#60;0.001), as indicated by a decrease in the expression levels of collagen I and collagen IV in lung tissue (both P&#60;0.001). Angiogenesis (as shown by CD31 immunohistochemistry) was also decreased (P&#60;0.01). In irradiated mice, Endostar inhibited the transforming growth factor-&#946;1 (TGF-&#946;1)/drosophila mothers against the decapentaplegic 3 (Smad3)/extracellular regulated protein kinases (ERK) signaling pathway (all P&#60;0.05). In vitro, Endostar treatment decreased the radiation-induced expression of TGF-&#946;1, vascular endothelial growth factor (VEGF), p-Smad3, and p-ERK in alveolar epithelial cells and vascular endothelial cells (all P&#60;0.05). <p> Conclusion: Endostar could alleviate RIPF through decreased antiangiogenic activity and inhibition of the TGF-&#946;1/Smad3/ERK pathway.</p>


Endostar, radiation-induced pulmonary fibrosis, angiogenesis, transforming growth factor-&#946;1.


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