The positive role of vitronectin in radiation induced lung toxicity: the in vitro and in vivo mechanism study

Tian-Le Shen, Mi-Na Liu, Qin Zhang, Wen Feng, Wen Yu, Xiao-Long Fu, Xu-Wei Cai

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. 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. 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. 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.