Serum exosomes from diabetic kidney disease patients promote pyroptosis and oxidative stress through the miR-4449/HIC1 pathway

Abstract

BACKGROUND: Diabetic kidney disease (DKD) is a major contributor to end-stage renal disease. Several microRNAs (miRNAs) have been found to be enriched in exosomes of DKD patients, but it remains unclear if any of these miRNAs play an important role in the pathogenesis of DKD. METHODS: Exosomes from diabetic kidney disease (DKD) patients were isolated, and the expression of miR-4449 was measured by qRT-PCR. Reactive oxygen species (ROS) was determined by DCDFA assay kit, and pyroptosis was measured by quantifying the level of activated caspase 1. mRNA and protein levels were quantified by qRT-PCR and WB. RESULTS: In this study, we demonstrated that miR-4449 is enriched in the serum exosomes of DKD patients, and these exosomes regulate the expression of pro-inflammatory cytokines, ROS levels, and pyroptosis through miR-4449. CONCLUSIONS: Our study uncovered a novel mechanism for the progression of DKD that is mediated through miR-4449 in serum exosomes, which highlights an important role for exosomes in the pathogenesis of DKD.