Skip to main content
main-content

01.12.2018 | Research | Ausgabe 1/2018 Open Access

Journal of Translational Medicine 1/2018

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

Zeitschrift:
Journal of Translational Medicine > Ausgabe 1/2018
Autoren:
Tian-Le Shen, Mi-Na Liu, Qin Zhang, Wen Feng, Wen Yu, Xiao-Long Fu, Xu-Wei Cai
Wichtige Hinweise

Electronic supplementary material

The online version of this article (https://​doi.​org/​10.​1186/​s12967-018-1474-y) contains supplementary material, which is available to authorized users.

Abstract

Background

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.

Methods

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.

Results

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.

Conclusions

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.
Zusatzmaterial
Literatur
Über diesen Artikel

Weitere Artikel der Ausgabe 1/2018

Journal of Translational Medicine 1/2018 Zur Ausgabe