Rosmarinic acid alleviates radiation-induced pulmonary fibrosis by downregulating tRNA N7-Methylguanosine modification-regulated fibroblast to myofibroblast transition through the exosomes pathway

Abstract

Abstract Background Radiation-induced pulmonary fibrosis (RIPF) is a common complication after radiotherapy in thoracic cancer patients, and there is a lack of effective treatment methods. The aim of this study was to explore the protective effect of rosmarinic acid (RA) on RIPF in mice as well as the underlying mechanism. Results We found that RA exerted an antifibrotic effect on lung tissues of RIPF mouse models and inhibited the progression of FMT through exosomes derived from lung epithelial cells. Mechanistically, RA reduced the transcription and translation efficiency of SPHK1 in lung fibroblasts by decreasing the tRNA N7-methylguanosine modification and downregulating the expression of tRNAs in lung epithelial cell-derived exosomes after irradiation, as well as inhibiting the interaction of SPHK1 with the NAT10 protein in fibroblasts. Furthermore, exosomes derived from irradiated lung epithelial cells after RA intervention decreased the acetylation and cytoplasmic translocation of PFKFB3, suppressing the FMT process triggered by glycolysis, and ultimately decelerating the progression of RIPF. Conclusions These findings suggest RA as a potential therapeutic agent for RIPF.