Bone marrow mesenchymal stem cells protect against radiation-induced lung injury by regulating AngII/ACE2/Ang(1-7) axis

Abstract Background Radiation-induced lung injury (RILI) is one of the most common complications of thoracic tumors radiotherapy. Since therapeutic strategies remains limited, the exploration of new approaches to treat RILI is on high demands. The use of bone mesenchymal stem cells (BMSCs) to treat RILI holds great promise. Here, we investigate the therapeutic potential of BMSCs in RILI. Methods C57BL/6 mice received thoracic irradiation except for the control group.Within 24 hours after irradiation, BMSCs were injected via the tail vein in BMSCs group. At 5 weeks after irradiation, H&E staining and immunohistochemistry were used to observe the pathological changes of lung tissue and the expression of inflammatory factors. Electron microscopy was used to detect changes in cell structure.Immunofluorescence and western blot were uesd to detect the expression of ACE2, ACE and AT1R.. The expression of Ang II and Ang (1-7) was detected by ELISA. The expression of MasR mRNA in lung tissue was detected by qRT-PCR. Results we found that radiation obviously caused lung tissue injury, especially alveolar type II epithelial cells by H&E and electron microscopy. Immunofluorescence and western blot showed that ACE2 decreased significantly in irradiation group. After BMSCs injection, BMSCs significantly reduced RILI by H&E and immunohistochemistry. Immunofluorescence results showed that BMSCs migrated to injuried lung tissue and differentiated into alveolar type II epithelial cells to up-regulated AngII/ACE2/Ang(1-7) axis.Conclusions The study demonstrated that BMSCs may be transplanted into damaged lung tissue where they differentiated into AEC II to regulated AngII/ACE2/Ang(1-7) axis to alleviate RILI.