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- Title
The positive role of vitronectin in radiation induced lung toxicity: the in vitro and in vivo mechanism study.
- Authors
Shen, Tian-Le; Liu, Mi-Na; Zhang, Qin; Feng, Wen; Yu, Wen; Fu, Xiao-Long; Cai, Xu-Wei
- Abstract
<bold>Background: </bold>Radiation-induced lung toxicity (RILT) is a severe complication of radiotherapy in patients with thoracic tumors. Through proteomics, we have previously identified vitronectin (VTN) as a potential biomarker for patients with lung toxicity of grade ≥ 2 radiation. Herein, we explored the molecular mechanism of VTN in the process of RILT.<bold>Methods: </bold>In this study, lentivirus encoding for VTN and VTN-specific siRNA were constructed and transfected into the cultured fibroblasts and C57BL mice. Real-time PCR, western blot and ELISA were used to examine expression of collagens and several potential proteins involved in lung fibrosis. Hematoxylin-eosin and immunohistochemical staining were used to assess the fibrosis scores of lung tissue from mice received irradiation.<bold>Results: </bold>The expression of VTN was up-regulated by irradiation. The change trend of collagens, TGF-β expression and p-ERK, p-AKT, and p-JNK expression levels were positively related with VTN mRNA level. Furthermore, overexpression of VTN significantly increased the expression level of α-SMA, as well as the degree of lung fibrosis in mice at 8 and 12 weeks post-irradiation. By contrast, siRNA VTN induced opposite results both in vitro and in vivo.<bold>Conclusions: </bold>VTN played a positive role in the lung fibrosis of RILT, possibly through modulation of fibrosis regulatory pathways and up-regulating the expression levels of fibrosis-related genes. Taken together, all the results suggested that VTN had a novel therapeutic potential for the treatment of RILT.
- Subjects
RADIATION-induced abnormalities; VITRONECTIN; FIBROBLASTS; PULMONARY fibrosis; COLLAGEN
- Publication
Journal of Translational Medicine, 2018, Vol 16, Issue 1, pN.PAG
- ISSN
1479-5876
- Publication type
journal article
- DOI
10.1186/s12967-018-1474-y