Engineered RGD‐Treg‐Exos Targeted Delivery of miR‐218‐5p to Activate Mitophagy and Attenuate Podocyte Injury in Diabetic Kidney Disease
Zhaochen Guo, Shaohui Gao, Ziyue Wang, Zige Chen, Jinglei Chen, Aiping Duan, Feng Xu, Qinger Wang, Weisong Qin, Zeng Caihong, Zhihong Liu, Hao Bao
Abstract
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.