OP30 Human umbilical cord mesenchymal stem cells derived exosomes alleviate Ulcerative Colitis by inhibiting macrophage ferroptosis via miR-23b-3p/Nrf2 pathway

Abstract Background Human umbilical cord mesenchymal stem cell derived exosomes (HucMSC-Exo) have broad application prospects in treatment of various disease, including ulcerative colitis (UC). Macrophages can trigger intestinal mucosal inflammation thereby participating the onset and development UC. As a newly discovered iron-dependent death pathway, ferroptosis has also been found accompanied by inflammatory response recent studies. We speculated that there could be relationship between macrophage Furthermore, role process HucMSC-Exo alleviating UC remains undefined. This study aims to explore therapeutic effect mechanism on regulating ferroptosis. Methods The gene expression ferroptosis-related proteins was assessed colon samples from healthy controls patients In vivo, induced dextran sulfate sodium mice. administered intravenously estimate its curative effect, gut homing evaluated animal live imaging analysis. vitro, were cocultured with inducer RSL3-treated bone marrow-derived macrophages (BMDMs), RAW264.7 line, followed examining HucMSC-Exo. Transfection microRNA mimics knockdown used confirm miR-23b-3p Results Compared individuals, may involved patients. successfully target damaged tissues vivo. significantly improved pathological damage tissue, increased glutathione peroxidase 4 (GPX4), while markedly decreasing levels iron lipid ROS, reducing secretion interleukin (IL)-1β IL-6, then relieved alleviate murine colitis. vitro experiments showed effectively absorbed rescued RSL3-induced ferroptosis, which consistent ferrostatin-1, ferroptosis-specifific inhibitor. Mechanismly, HucMSC-exo inhibit delivering highly expressed activate Nrf2 pathway. Additionally, protection for attenuated or inhibiting Conclusion antioxidant pathway abrogate ultimately ameliorate