biostudies-literatureGuo ZKey Research and Development Program of Jiangsu ProvinceMedical Research Project of Jiangsu Commission of HealthMedical Innovation Center of Kidney Diseasee12034https://www.ebi.ac.uk/biostudies/studies/S-EPMC12499504biostudies-literatureUnknown12(37)Diabetic kidney disease (DKD) is the main cause of end-stage kidney disease, and podocyte injury is an important factor in the development of DKD. Mitophagy is severely inhibited in the podocytes of patients. Damaged mitochondria aggregate in the cytoplasm and can not be removed effectively. Restoring mitophagy may be a novel strategy for the treatment of DKD. In this study, Regulatory T cells (Tregs) are found to reduce podocyte injury in DKD through exosomes. Sequencing and cross-sectional analysis revealed that exosomes from Tregs delivered miR-218-5p to increase mitophagy in podocytes by inhibiting the TNC/TLR4/SRC/FUNDC1 pathway. Treg-Exos are engineered to express RGD peptides on the membrane surface. RGD-Treg-Exos bind to integrins on the surface of podocytes and effectively target podocytes for the delivery of miR-218-5p, thus increasing mitophagy in podocytes, reducing cell apoptosis, and alleviating podocyte injury. In summary, this study revealed that engineered RGD-Treg-Exos effectively ameliorated podocyte injury in DKD, thus constituting a novel method for DKD treatment.Advanced science (Weinheim, Baden-Wurttemberg, Germany)Engineered RGD-Treg-Exos Targeted Delivery of miR-218-5p to Activate Mitophagy and Attenuate Podocyte Injury in Diabetic Kidney Disease.PMC12499504BE2022825CXZX202202K2023003Zeng CLiu ZGuo ZWang QChen ZChen JDuan ABao HXu FQin WWang ZGao SfalseEngineered RGD-Treg-Exos Targeted Delivery of miR-218-5p to Activate Mitophagy and Attenuate Podocyte Injury in Diabetic Kidney Disease.Diabetic kidney disease (DKD) is the main cause of end-stage kidney disease, and podocyte injury is an important factor in the development of DKD. Mitophagy is severely inhibited in the podocytes of patients. Damaged mitochondria aggregate in the cytoplasm and can not be removed effectively. Restoring mitophagy may be a novel strategy for the treatment of DKD. In this study, Regulatory T cells (Tregs) are found to reduce podocyte injury in DKD through exosomes. Sequencing and cross-sectional analysis revealed that exosomes from Tregs delivered miR-218-5p to increase mitophagy in podocytes by inhibiting the TNC/TLR4/SRC/FUNDC1 pathway. Treg-Exos are engineered to express RGD peptides on the membrane surface. RGD-Treg-Exos bind to integrins on the surface of podocytes and effectively target podocytes for the delivery of miR-218-5p, thus increasing mitophagy in podocytes, reducing cell apoptosis, and alleviating podocyte injury. In summary, this study revealed that engineered RGD-Treg-Exos effectively ameliorated podocyte injury in DKD, thus constituting a novel method for DKD treatment.2025-01-01T00:00:00Z2025 Oct2026-06-04T04:48:09.157Z2026-05-05T03:12:34.95ZS-EPMC124995044082765710.1002/advs.202412034