Plasma Exosomal circRNAs as Potential Biomarkers for Patients with Septic Shock-Induced Acute Kidney Injury.

Abstract

Sepsis-induced acute kidney injury (AKI) is marked by high mortality and poor prognosis. Recent studies suggest that exosomal circRNAs regulate key pathways involved in inflammation, oxidative stress, and apoptosis, processes central to sepsis-induced AKI. This study investigates the differential expression of exosomal circRNAs and their functional implications in the pathogenesis of sepsis-induced AKI. Patients with sepsis-induced AKI and healthy volunteers were recruited for the research. Whole blood samples were collected, and exosomes were isolated and characterized through particle detection, transmission electron microscopy, and Western blot for exosomal marker proteins. Real-time PCR was used to analyze exosomal circRNAs, including circ-Fryl, circ-TLK1, circ-PTK2, circ-Ttc3, circ-VMA21, and circ_0091702. Additionally, assays were performed to assess cell proliferation, apoptosis, and uptake in HK-2 cells exposed to exosomes from both control and sepsis-induced AKI samples. Seven patients with sepsis-induced AKI and six healthy individuals were enrolled. Exosomal protein markers were analyzed from plasma samples of both groups. Exosomes from the sepsis-induced AKI group (mean particle diameter: 146.1 nm) and the control group (mean particle diameter: 150.9 nm) exhibited a characteristic spherical morphology. Plasma levels of circ-Ttc3 (p < 0.05), circ-Fryl (p < 0.01), and circ_0091702 (p < 0.01) were notably lower in the sepsis-induced AKI group relative to the control group. Additionally, HK-2 cells exposed to sepsis-induced AKI exosomes showed upregulation of circ-Ttc3 and downregulation of circ-TLK1. Following exposure to sepsis-induced AKI exosomes, HK-2 cell viability decreased while apoptosis increased. circRNAs such as circ-Ttc3, circ-TLK1, circ-Fryl, and circ_0091702 hold potential as candidate biomarkers and therapeutic targets for sepsis-induced AKI.