Geranylgeranylacetone alleviates radiation-induced lung injury by inhibiting epithelial-to-mesenchymal transition signaling

Abstract

Radiation-induced lung injury (RILI) involves pneumonitis and fibrosis, and results in pulmonary dysfunction. Moreover, RILI can be a fatal complication of thoracic radiotherapy. The present study investigated the protective effect of geranylgeranlyacetone (GGA), an inducer of heat shock protein (HSP)70, on RILI using a C57BL/6 mouse model of RILI developing 6 months subsequent to exposure to 12.5 Gy thoracic radiation. GGA was administered 5 times orally prior and subsequent to radiation exposure, and the results were assessed by histological analysis and western blotting. The results show that late RILI was alleviated by GGA treatment, possibly through the suppression of epithelial-to-mesenchymal transition (EMT) marker expression. Based on histological examination, orally administered GGA during the acute phase of radiation injury not only significantly inhibited pro-surfactant protein C (pro-SPC) and vimentin expression, but also preserved E-cadherin expression 6 months after irradiation-induced injury of the lungs. GGA induced HSP70 and inhibited EMT marker expression in L132 human lung epithelial cells following IR. These data suggest that the prevention of EMT signaling is a key cytoprotective effect in the context of RILI. Thus, HSP70-inducing drugs, such as GGA, could be beneficial for protection against RILI.