Abstract
Pulmonary fibrosis is one of the most severe late-onset lung injuries resulting from radiation therapy. We previously reported a strain difference in the incidence rate of pulmonary fibrosis induced by carbon-ion irradiation in the mouse model. Determining the cause of this difference could aid the development of prevention and treatment strategies that consider the individual variations in pulmonary fibrosis induced by carbon-ion therapy. Although collapse of the expression balance among MMP2, MMP9, and TIMP1 has been reported in a bleomycin-induced fibrosis model, the roles of these factors in radiation-induced fibrosis are not fully understood. In this study, we analyzed the expression of MMP2, MMP9, and TIMP1 in pulmonary fibrosis induced by carbon-ion irradiation.
The lungs of two mouse strains (C57Bl/6J and C3H/He) were irradiated by carbon-ion irradiation at 10 Gy. Pulmonary fibrosis was observed in all C57Bl/6J mice at 24 weeks after the irradiation and was exacerbated at 28 weeks. On the other hand, pulmonary fibrosis was also observed in only three of five C3H/He mice at 24 weeks, with none apparent at 28 weeks. These results suggested that pulmonary fibrosis continuously progressed in the C57Bl/6J mice, but that this injury could be improved in the C3H/He mice. We then investigated the expression of MMP2, MMP9, and TIMP1 in the cases of pulmonary fibrosis by real-time PCR and immunohistochemistry. The levels of MMP9 expression in the fibrotic area differed significantly between the two strains, although the expression of MMP2 and TIMP1 was upregulated throughout the lungs of both strains. Herein we present our comparative analysis of the observed strain difference in both MMP expression and progression of pulmonary fibrosis induced by carbon-ion irradiation.
