Tubular epithelial cells derived-exosomes containing CD26 protects mice against renal ischemia/reperfusion injury by maintaining proliferation and dissipating inflammation

Ischemia-reperfusion injury (IR) is the leading cause of acute kidney injury (AKI). No effective drugs to treat IR-related AKI are currently available. Recent pre-clinical trials have evaluated the therapeutic potential of extracellular vesicles-exosomes to chronic kidney disease. Here, we found exosomes derived from the tubular epithelial cell in IR condition (Exo(IR)) enriched CD26, compared with control (Exo(Normal)). Tracking exosomes in vivo certified tubular epithelial cell uptake exosomes. We have isolated exosomes with overexpression of CD26 (Exo(CD26+)) from culture media from tubular epithelial cell line transferred by adenovirus vectors. After administration of exosomes (100 mg) or bovine serum albumin (BSA, equivalent protein control) in IR or sham operation mice after 72 h via tail vein injection, the renal function impairment and histology injury were relived in mice receiving Exo(CD26+). Immunofluorescence staining with proliferating cell nuclear antigen revealed Exo(CD26+) recovered proliferation of cells partly after IR injury. Cell cycle modulator, p53 and p21 were upregulated in IR mice receiving BSA control, Exo(Normal), and Exo(IR). Exo(CD26+) significantly blunt this protein upregulation. Inflammatory cell infiltration and chemokine receptor (CXCR4) were dissipated in IR mice receiving Exo(CD26+). Downstream chemokine of CXCR4, stromal derived factor-1 (SDF1) also decreased after administration of Exo(CD26+) in IR mice. Finally, Exo(CD26+) suppressed inundant collagenI expression in IR kidney. In conclusion, Tubular epithelial cells derived-exosomes containing CD26 might be one of the therapy modes for IR-AKI by maintaining proliferation and dissipating inflammation. (C) 2021 The Authors. Published by Elsevier Inc.

Automated summary

Ischemia-reperfusion injury (IR) is a major cause of acute kidney injury (AKI), and currently there are no effective drugs for it. Exosomes derived from tubular epithelial cells under IR conditions may hold therapeutic potential for IR-related AKI by promoting cell proliferation and reducing inflammation. Further research is needed to explore the clinical applications of these exosomes in treating AKI.