Diagnostic value of miR-126-5p in sepsis-induced acute kidney injury and its molecular mechanism via CASP3

Background: As a common and devastating complication of sepsis, sepsis-induced acute kidney injury (SAKI) confers a significant risk of mortality. Purpose: This work focused on the utility of miR-126-5p as a biomarker for SAKI. Methods: A total of 95 patients with SAKI and 70 patients with sepsis alone were enrolled. Serum levels of miR-126-5p and Caspase-3 (CASP3) were measured using RT-qPCR. The regulatory interaction between miR-126-5p and CASP3 was validated using a dual-luciferase reporter assay. Cell proliferation, apoptosis, inflammatory cytokine levels, and oxidative stress markers were evaluated using the CCK-8 assay, flow cytometry, ELISA, and corresponding commercial kits, respectively. Results: Serum miR-126-5p levels were downregulated in SAKI patients and showed significant negative correlations with kidney injury markers, including serum creatinine (Scr), cystatin C (Cys-C), neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury molecule-1 (KIM-1). Overexpression of miR-126-5p in lipopolysaccharide (LPS)-stimulated HK-2 cells was shown in vitro to facilitate cell proliferation, restrain apoptosis, and suppress the production of interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α). Concurrently, it reduced oxidative stress markers, reactive oxygen species (ROS), and malondialdehyde (MDA), and enhanced superoxide dismutase (SOD) activity. Mechanistically, CASP3 was identified as a direct downstream target of miR-126-5p, and its expression was negatively regulated by miR-126-5p. Furthermore, overexpression of CASP3 significantly reversed the protective effects of miR-126-5p in vitro. Conclusions: MiR-126-5p showed diagnostic value for SAKI and exerted a protective effect in vitro through targeted regulation of CASP3 expression.