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GPR110-Dependent Macrophage Polarization Mediates the Therapeutic Effect of V-N3P Single-Atom Catalyst in Septic Intestinal Injury
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DOI：10.1016/j.biomaterials.2026.124436.png)
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Abstract
En 中文
Sepsis-induced intestinal injury is driven predominantly by disordered macrophage-mediated inflammatory responses.Vanadium-based single-atom catalysts (V-SACs) have been associated with the alleviation of inflammatory diseases because of their excellent redox catalytic activity; however, their function in septic intestinal injury remains elusive. This study synthesized two coordination-defined SACs, V-N4 and V-N3P. Furthermore, their protective effects and molecular mechanisms were systematically explored via dual in vivo cecal ligation and puncture (CLP) murine and porcine sepsis models, as well as in vitro LPS-stimulated RAW264.7 macrophage cell line and primary bone marrow-derived macrophage (BMDM) inflammatory models. The data revealed that V-N3P had a superior reactive oxygen species scavenging ability than V-N4, attributed to phosphorus-induced charge delocalization, which improved its nanozyme activity. Moreover, in septic mice, V-N3P significantly improved survival rate, restored intestinal mucosal integrity, reduced pro-inflammatory cytokine levels, and upregulated tight junction proteins (Occludin, ZO-1) and MUC2, which also confirmed in the porcine sepsis model. In addition, V-N3P remodeled macrophage homeostasis to suppress M1 pro-inflammatory phenotype and facilitate M2 anti-inflammatory polarization, which also confirmed in vitro. Mechanistically, V-N3P was found to downregulate ROS via GPR110 to inhibit JNK/NF-κB/ERK pro-inflammatory signaling, and stimulate the A20/STAT3 anti-inflammatory axis. In conclusion, these data indicated that V-N3P mitigates septic intestinal injury by downregulating GPR110 to restore macrophage polarization, offering a coordination-defined V-N3P single-atom nanozyme-based therapeutic approach for septic intestinal injury with validation in both rodent and porcine models, providing a theoretical foundation for SAzyme-based immunomodulation
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12.9
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