Mmu_circ_0005698/hsa_circ_0085381/miR-532-3p/Arhgdib axis mediates the ischemic progression of acute kidney injury

Acute Kidney Injury (AKI) is a clinical syndrome characterized by a rapid decline in renal function. With significant epidemiological implications, AKI is prevalent worldwide and its incidence continues to rise annually. It is estimated that there are more than 13 million AKI individuals worldwide each year, resulting in approximately 1.7 million deaths. Globally, AKI occurs in 13–18 % of hospitalized patients, in 30–50 % of those in intensive care units (ICUs).Recent studies have indicated that certain circRNAs participate in acute kidney injury development, yet the precise mechanisms underlying their roles in ischemic AKI remain unclear. To address meet the urgent need to investigate the underlying mechanisms of AKI, identify new treatment strategies, and support early diagnosis and prevention of AKI, we conducted the study presented in this paper. This study presents the first report that mmu_circ_0005698 is upregulated following ischemia/reperfusion (I/R) treatment. From a functional perspective, mmu_circ_0005698 contributes to I/R-triggered apoptosis in BUMPT cells. Mechanistically, mmu_circ_0005698 enhances the expression of Rho GDP dissociation inhibitor β (Arhgdib) by sequestering miR-532-3p, thereby promoting apoptosis. Notably, silencing of mmu_circ_0005698 mitigates ischemic AKI advancement via the miR-532-3p/Arhgdib pathway. Finally, hsa_circ_0085381, which shares homology with mmu_circ_0005698, mediates I/R-triggered apoptosis in HK-2 cells by modulating the miR-532-3p/Arhgdib axis. Consequently, we propose that the mmu_circ_0005698 and hsa_circ_0085381/miR-532-3p/Arhgdib pathway plays a crucial role in ischemic AKI development, while hsa_circ_0085381 emerges as a promising therapeutic candidate for ischemic AKI treatment.