Diagnostic Value of miR-126-5p in Sepsis-Induced Acute Kidney Injury and its Molecular Mechanism via CASP3

As a common and devastating complication of sepsis, sepsis-induced acute kidney injury (SAKI) confers a significant risk of mortality.

This work focused on the utility of miR-126-5p as a biomarker for SAKI.

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 reverse transcription quantitative polymerase chain reaction. 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 cell counting kit-8 assay, flow cytometry, enzyme-linked immunosorbent assay, and corresponding commercial kits, respectively.

Serum miR-126-5p levels were downregulated in SAKI patients and showed significant negative correlations with kidney injury markers, including serum creatinine, cystatin C, neutrophil gelatinase-associated lipocalin, and kidney injury molecule-1. Overexpression of miR-126-5p in lipopolysaccharide-stimulated HK-2 cells was shown in vitro to facilitate cell proliferation, restrain apoptosis, and suppress the production of interleukin-1β, interleukin-6, and tumor necrosis factor-α. Concurrently, it reduced oxidative stress markers, reactive oxygen species, and malondialdehyde, and enhanced superoxide dismutase 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 .

miR-126-5p showed diagnostic value for SAKI and exerted a protective effect in vitro through targeted regulation of CASP3 expression.