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BioMed Research International
Volume 2017, Article ID 1279280, 10 pages
https://doi.org/10.1155/2017/1279280
Research Article

Pentoxifylline Regulates Plasminogen Activator Inhibitor-1 Expression and Protein Kinase A Phosphorylation in Radiation-Induced Lung Fibrosis

1Laboratory of Radiation Exposure & Therapeutics, National Radiation Emergency Medical Center, KIRAMS, Seoul, Republic of Korea
2Department of Pathology, Korea Cancer Center Hospital, KIRAMS, Seoul, Republic of Korea
3Molecular Imaging Research Center, KIRAMS, Seoul, Republic of Korea

Correspondence should be addressed to Sunhoo Park; rk.er.smarik@oohnus

Received 27 September 2016; Revised 30 December 2016; Accepted 19 January 2017; Published 27 February 2017

Academic Editor: Milton O. Moraes

Copyright © 2017 Jong-Geol Lee et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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.