Circular RNA Shows Protective Signals in Mouse and Cell Models of Sepsis-Linked Kidney Injury

Sepsis-induced acute kidney injury (SAKI) is a frequent and life-threatening complication that currently lacks standardized therapeutic strategies. A new study in Biological Procedures Online reports that a circular RNA called circ_0000745, previously found to be significantly downregulated in the serum of septic patients, showed protective signals in experimental models of this condition through a regulatory pathway involving microRNA-671-5p and insulin-like growth factor binding protein 3 (IGFBP3).

The researchers established a cecal ligation and puncture (CLP) mouse model and a lipopolysaccharide (LPS)-stimulated HK-2 cell model of SAKI, complemented by serum samples 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 authors report that circ_0000745 expression was consistently suppressed in the clinical SAKI samples, the CLP-treated mice, and the LPS-stimulated cells.

When the researchers enforced expression of circ_0000745 in vivo, they observed improved renal histology and renal-function indices and reduced pro-inflammatory cytokine concentrations in kidney homogenates. In the cell model, circ_0000745 overexpression improved cell viability and attenuated apoptosis, as assessed using histology, TUNEL staining, flow cytometry, ELISA, CCK-8 assays, and Western blotting.

Mechanistically, the study indicates that circ_0000745 functioned as a competing endogenous RNA by sequestering miR-671-5p, thereby relieving post-transcriptional repression of IGFBP3. Interactions among circ_0000745, miR-671-5p, and IGFBP3 were validated by dual-luciferase reporter and RNA pull-down assays, and rescue experiments supported involvement of this regulatory axis. Manipulation of the axis also altered the autophagy-related markers Beclin1, LC3, and SQSTM1/p62 in a pattern the authors describe as compatible with increased autophagy-related activity during the early injury phase.

The authors are careful to note limitations. Because lysosomal-blockade experiments were not performed, the static markers do not establish increased autophagic flux. The results indicate 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, but autophagic-flux assays and kidney-targeted models are required before direct renoprotective or autophagy-activating effects can be concluded.

Subject of Research: The role of the circular RNA circ_0000745 and the miR-671-5p/IGFBP3 axis in sepsis-induced acute kidney injury models

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

Article References: Wang, X., Wang, C., Wang, W., Li, H., Yao, Y., Gao, X., Peng, Y., Dong, H., Zhu, Z., & Kang, W. (2026). Circ_0000745 Attenuates Sepsis-Induced Acute Kidney Injury Via the MiR‑671‑5p/IGFBP3 Axis, with Associated Changes in Autophagy-Related Markers. Biological Procedures Online. https://doi.org/10.1186/s12575-026-00365-x

Image Credits: AI Generated

DOI: 10.1186/s12575-026-00365-x

Keywords: sepsis, acute kidney injury, circular RNA, circ_0000745, miR-671-5p, IGFBP3, autophagy markers, CLP mouse model, HK-2 cells, competing endogenous RNA, inflammation, apoptosis