Circ_0000745 Attenuates Sepsis-Induced Acute Kidney Injury Via the MiR‑671‑5p/IGFBP3 Axis, with Associated Changes in Autophagy-Related Markers

Sepsis-induced acute kidney injury (SAKI) is a frequent and life-threatening complication that currently lacks standardized therapeutic strategies. Circular RNAs have emerged as critical regulators in SAKI pathogenesis, and circ_0000745 has been identified as significantly downregulated in the serum of septic patients. A cecal ligation and puncture (CLP) mouse model and a lipopolysaccharide (LPS)-stimulated HK-2 cell model of SAKI were established, complemented by serum from 15 patients with SAKI and 15 matched healthy controls. circ_0000745 expression and localization were profiled by RT-qPCR and fluorescence in situ hybridization. The effects of circ_0000745 overexpression on renal injury, apoptosis, inflammation, and static autophagy-related markers were assessed using histology, TUNEL, flow cytometry, ELISA, CCK-8, and Western blotting. Interactions among circ_0000745, miR-671-5p, and IGFBP3 were validated by dual-luciferase reporter and RNA pull-down assays, with rescue experiments supporting involvement of the regulatory axis. Circ_0000745 expression was consistently suppressed in clinical SAKI samples, CLP-treated mice, and LPS-stimulated cells. Enforced expression of circ_0000745 in vivo improved renal histology and renal-function indices and reduced pro-inflammatory cytokine concentrations in kidney homogenates. In vitro, circ_0000745 overexpression improved cell viability and attenuated apoptosis. Mechanistically, circ_0000745 functioned as a competing endogenous RNA by sequestering miR-671-5p, thereby relieving post-transcriptional repression of insulin-like growth factor binding protein 3 (IGFBP3). Manipulation of the circ_0000745/miR-671-5p/IGFBP3 axis also altered Beclin1, LC3, and SQSTM1/p62 in a pattern compatible with increased autophagy-related activity during the early injury phase. Because lysosomal-blockade experiments were not performed, these static markers do not establish increased autophagic flux. Our results indicated that circ_0000745 attenuated measured renal and cellular injury endpoints in the experimental SAKI models through the miR-671-5p/IGFBP3 axis and was associated with favorable changes in static autophagy-related markers. Autophagic-flux assays and kidney-targeted models are required before direct renoprotective or autophagy-activating effects can be concluded.