Predictive value of miR-582-5p for onset of sepsis-induced acute kidney injury and its functional role during disease development.

Abstract

Introduction: Acute kidney injury (AKI) is a common complication of sepsis, characterized by sharply declining renal function. As a global concern, understanding its pathogenesis and improving diagnosis and therapy face significant challenges. MicroRNAs are involved in the progression of a variety of diseases.This research was focused on differences in expression and clinical predictive value of miR-582-5p in sepsis-induced AKI.

Material and methods: Blood and urine samples were collected from 180 patients. Sepsis-induced AKI was imitated in vitro by human kidney 2 (HK2) cells treated with 10 µg/ml lipopolysaccharide (LPS). The relative expression of miR-582-5p and HMGB2 in different conditions was quantified by qRT-PCR. Regulation of gene expression was performed by cell transfection. Cell viability and apoptosis were detected subsequently. Kidney injury and inflammatory assessment were analyzed by means of ELISA. Estimation of oxidative stress was performed using the corresponding kit. The dual luciferase reporter system verified the targeting relationship between miR-582-5p and HMGB2.

Results: Relative expression of miR-582-5p was lower in sepsis patients who suffered AKI later, along with LPS-induced HK2 cells. Both weak viability and elevated apoptosis were reversed by up-regulated miR-582-5p in HK2 cells exposed to LPS. In addition, the concentration of inflammatory factors and oxidation levels showed a significant decrease, based on up-regulated miR-582-5p. The clinical predictive value of miR-582-5p was visualized by a ROC curve with high sensitivity and specificity.

Conclusions: Up-regulated miR-582-5p reduced sepsis-induced AKI, and HMGB2 was a potential downstream target of miR-582-5p.