Ultrasound-Modulated Macrophages Inhibit Keloid Formation Via Egr1

This study investigates ultrasound-mediated macrophage reprogramming through the Egr1/Thbs1 axis to suppress keloid formation, aiming to establish a macrophage-targeted therapeutic strategy for pathological scar management. Using in vitro macrophage-ECM models and keloid-prone animal models, we combined transcriptomic/proteomic profiling, myeloid-specific Egr1 knockout mice, and functional assays. Ultrasound parameters were optimized to modulate macrophage phenotypes, with validation via molecular biology and multi-omics analyses. Ultrasound reversed pro-fibrotic macrophage activation induced by high ECM stiffness, inhibiting macrophage-to-myofibroblast transition (MMT) and keloid progression. Mechanistically, ultrasound downregulated Egr1 expression and its downstream target Thbs1, disrupting fibrotic signaling. Myeloid Egr1 deletion mimicked ultrasound effects, confirming its regulatory role. The Egr1/Thbs1 axis is critical for ultrasound-driven macrophage reprogramming and keloid suppression. This work proposes a non-invasive ultrasound paradigm targeting macrophage plasticity, offering a mechanistic foundation for clinical translation.