Exosomal miR ‐7002‐5p derived from highglucose‐induced macrophages suppresses autophagy in tubular epithelial cells by targeting Atg9b

Abstract Macrophage infiltration plays an important role in the progression of diabetic nephropathy (DN). Previously, we demonstrated that highglucose‐stimulated macrophage‐derived exosomes (HG‐exo) induces proliferation and extracellular matrix accumulation in glomerular mesangial cells, but its effect on tubular cells is unclear. This study aimed to explore the role of HG‐exo on renal tubular injury in DN. The results show that HG‐exo could induce dysfunction, autophagy inhibition, and inflammation in mouse tubular epithelial cell (mTEC) and C57 mouse kidney. Moreover, miR‐7002‐5p was differentially expressed in HG‐exo based on miRNAs sequencing and bioinformatics analysis. A dual‐luciferase reporter assay confirmed that Atg9b was the direct target gene of miR‐7002‐5p. Further experimentation showed that miR‐7002‐5p inhibition in vivo and vitro reserves HG‐exo effects. These results demonstrated that HG‐exo carries excessive miR‐7002‐5p and inhibits autophagy through targeting Atg9b; this process then induces renal tubular dysfunction and inflammation. In conclusion, our study clarifies the important role of macrophage‐derived exosomes in DN and is expected to provide new insight on DN prevention and treatment.