Abstract
Tubule injury is a characteristic pathological feature of acute kidney injury (AKI) and determines the prognosis of kidney disease. However, the exact mechanism of tubule injury remains largely unclear. In the present study, the exact mechanism of tubule injury was investigated. Bilateral renal ischemia/reperfusion (I/R) injury (I/RI) was induced in mice and exosome secretion inhibitor GW4869 and miRNA‑155 inhibitor were used. In addition, the exosomal microRNA (miR)‑155‑mediated cross‑talk between macrophage and tubular cells was also investigated. It was determined that tubular injury was observed in an I/R‑induced AKI model, which was closely associated with macrophage infiltration. Interestingly, blocking exosome production using GW4869 ameliorated tubular injury in I/R‑induced AKI. Mechanistically, once released, activated macrophage‑derived exosomal miR‑155 was internalized by tubular cells, resulting in increased tubule injury through targeting of suppressor of cytokine signaling‑1 (SOCS‑1), a negative regulator of NF‑κB signaling. In addition, a dual‑luciferase reporter assay confirmed that SOCS‑1 was the direct target of miR‑155 in tubular cells. Notably, injection of these miR‑155‑enriched exosomes into renal parenchyma resulted in increased tubule injury in vivo. Thus, the present study demonstrated that exosomal miR‑155 mediated the communication between activated macrophages and injured tubules, leading to progression of AKI, which not only provide novel insights into the pathophysiology of AKI but also offer a new therapeutic strategy for kidney diseases.