Abstract
Skin damage caused by radiation therapy (radiodermatitis) is a severe side effect of radiotherapy in cancer patients, and there is currently a lack of effective strategies to prevent or treat such skin damage. In this work, we show with several lines of evidence that plasminogen, a pro-inflammatory factor, is key for the development of radiodermatitis. After skin irradiation in wild-type (plg+/+) mice, the plasminogen level increased in the irradiated area, leading to severe skin damage such as ulcer formation. However, plasminogen-deficient (plg−/−) mice and mice lacking plasminogen activators were mostly resistant to radiodermatitis. Moreover, treatment with a plasminogen inhibitor, tranexamic acid, decreased radiodermatitis in plg+/+ mice and prevented radiodermatitis in plg+/− mice. Together with studies at the molecular level, we report that plasmin is required for the induction of inflammation after irradiation that leads to radiodermatitis, and we propose that inhibition of plasminogen activation can be a novel treatment strategy to reduce and prevent the occurrence of radiodermatitis in patients.
Highlights
50% of cancer patients receive some form of radiotherapy as a sole treatment or in combination with surgery or chemotherapy
Because we previously showed that plasminogen is a pro-inflammatory regulator[12], we tested the hypothesis that plasminogen is involved in the development of radiodermatitis
We found that the development of radiodermatitis in mice is initiated by the accumulation of plasminogen in the irradiated skin where it is activated to plasmin
Summary
50% of cancer patients receive some form of radiotherapy as a sole treatment or in combination with surgery or chemotherapy. Radiotherapy techniques are continuously being developed, most patients still suffer from radiation-induced side effects which are mostly seen in tissues with rapidly proliferating cells such as the skin, gastrointestinal tract, and bone marrow[1]. The skin is affected to various degrees after any form of radiotherapy. The earliest visible skin reaction is erythema, which occurs in 90% of patients, and this can later evolve into desquamation or even into ulcers[2]. Radiation-induced dermatitis can be very painful and can severely affect the patient’s life quality[3].
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