방사선의학 웹진

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Abstract

Purpose. Radiation-induced lung fibrosis (RILF) is a serious late complication of radiotherapy. In vitro studies have demonstrated that pentoxifylline (PTX) has suppressing effects in extracellular matrix production in fibroblasts, while the antifibrotic action of PTX alone using clinical dose is yet unexplored. Materials and Methods. We used micro-computed tomography (micro-CT) and histopathological analysis to evaluate the antifibrotic effects of PTX in a rat model of RILF. Results. Micro-CT findings showed that lung density, volume loss, and mediastinal shift are significantly increased at 16 weeks after irradiation. Simultaneously, histological analysis demonstrated thickening of alveolar walls, destruction of alveolar structures, and excessive collagen deposition in the irradiated lung. PTX treatment effectively attenuated the fibrotic changes based on both micro-CT and histopathological analyses. Western analysis also revealed increased levels of plasminogen activator inhibitor- (PAI-) 1 and fibronectin (FN) and PTX treatment reduced expression of PAI-1 and FN by restoring protein kinase A (PKA) phosphorylation but not TGF-β/Smad in both irradiated lung tissues and epithelial cells. Conclusions. Our results demonstrate the antifibrotic effect of PTX on radiation-induced lung fibrosis and its effect on modulation of PKA and PAI-1 expression as possible antifibrotic mechanisms.

Author information

Lee JG1, Shim S1, Kim MJ1, Myung JK2, Jang WS1, Bae CH1, Lee SJ1, Kim KM3, Jin YW1, Lee SS2, Park S2.​

1 Laboratory of Radiation Exposure & Therapeutics, National Radiation Emergency Medical Center, KIRAMS, Seoul, Republic of Korea.

2 Laboratory of Radiation Exposure & Therapeutics, National Radiation Emergency Medical Center, KIRAMS, Seoul, Republic of Korea; Department of Pathology, Korea Cancer Center Hospital, KIRAMS, Seoul, Republic of Korea.

3 Molecular Imaging Research Center, KIRAMS, Seoul, Republic of Korea.