Transcriptomics-Coupled Proteomics Identifies CD36 as a Potential Radiation-Responsive Biomarker in Macrophages

Abstract The therapeutic effect of radiotherapy is greatly hindered by radiation injury, primarily driven by a dysfunctional immune microenvironment. Macrophages play an essential role in regulating the radiation response, but their intrinsic mechanism is not fully understood. In this study, we aimed to identify key molecular targets underlying macrophage responses to radiation using omics technologies including transcriptomics and proteomics. We found that the mRNA and protein expression levels of the scavenger receptor CD36 (also known as fatty acid translocase) were significantly upregulated following radiation exposure in both the murine macrophage cell line RAW264.7 and primary mouse bone-marrow-derived macrophages. Additionally, in vivo experiments also confirmed a significant increase in the level of expression of CD36 in macrophages derived from mice exposed to radiation. Pharmacological inhibition of CD36 promoted radiation-induced macrophage apoptosis and inflammatory responses, indicating potential radioprotective and anti-inflammatory effects. These findings suggest that CD36 upregulation is a prominent feature of macrophages in response to radiation exposure, thereby highlighting its potential as a therapeutic target for mitigating radiation-induced injury.