Mmu_Circ_0001022/hsa_Circ_0056869-miRNA-92a-2-5p/SKI axis suppressed the progression of sepsis-associated acute kidney injury

Sepsis -associated acute kidney injury (SA-AKI) contributes substantially to mortality and morbidity in critically ill individuals. Although considerable investigation has been conducted, effective therapeutic strategies preventing its advancement remain unavailable, highlighting the importance of understanding its fundamental mechanisms. Previous research identified mmu_circ_26986/hsa_circ_0072463 as a prospective biomarker and treatment target for SA-AKI. The current investigation reveals that mmu_circ_0001022 displays increased expression in BUMPT cells(Boston University Mouse Proximal Tubular Epithelial cell line)and C57BL/6 mouse kidneys following lipopolysaccharide (LPS) exposure and cecal ligation and puncture (CLP). Experimental analyses indicate that mmu_circ_0001022 diminishes LPS-triggered apoptosis in BUMPT cells. The molecular mechanism involves sequestering miRNA-92a-2-5p, subsequently enhancing SKI expression. Enhanced mmu_circ_0001022 expression reduces CLP-initiated acute kidney injury (AKI) progression through the miRNA-92a-2-5p/SKI pathway. Research demonstrates that hsa_ circ_0056869, the mmu_circ_0001022 homologous form, reduces LPS-initiated apoptosis in HK-2 cells (Human Kidney 2 cell line) via the miRNA-92a-2-5p/SKI pathway. Notably, septic patients experiencing AKI demonstrated elevated hsa_circ_0056869 plasma concentrations versus non-AKI cases. Analysis revealed hsa_circ_0056869 exhibited 79.41 % sensitivity, 82.35 % specificity, and 0.8175 area under the curve. A marked positive association emerged between hsa_circ_0056869 plasma levels and serum creatinine in septic individuals (r = 0.786). These findings establish the mmu_circ_0001022/hsa_circ_0056869-miRNA-92a-2-5p/SKI pathway as significant in SA-AKI pathogenesis. In addition, our data indicate that hsa_circ_0056869 may serve as an early diagnosis marker for the septic AKI.