Tubulointerstitial
inflammation is a common characteristic of acute and chronic kidney injury. However, the mechanism by which the initial injury of tubular epithelial cells (TECs) drives interstitial
inflammation remains unclear. This paper aims to explore the role of exosomal
miRNAs derived from TECs in the development of tubulointerstitial
inflammation. Global
microRNA(
miRNA) expression profiling of renal exosomes was examined in a LPS induced
acute kidney injury (AKI) mouse model and miR-19b-3p was identified as the
miRNA that was most notably increased in TEC-derived exosomes compared to controls. Similar results were also found in an
adriamycin (ADR) induced chronic proteinuric
kidney disease model in which exosomal miR-19b-3p was markedly released. Interestingly, once released, TEC-derived exosomal miR-19b-3p was internalized by macrophages, leading to M1 phenotype polarization through targeting NF-κB/SOCS-1. A dual-
luciferase reporter assay confirmed that SOCS-1 was the direct target of miR-19b-3p. Importantly, the pathogenic role of exosomal miR-19b-3p in initiating renal
inflammation was revealed by the ability of adoptively transferred of purified TEC-derived exosomes to cause tubulointerstitial
inflammation in mice, which was reversed by inhibition of miR-19b-3p. Clinically, high levels of miR-19b-3p were found in urinary exosomes and were correlated with the severity of tubulointerstitial
inflammation in patients with
diabetic nephropathy. Thus, our studies demonstrated that exosomal miR-19b-3p mediated the communication between injured TECs and macrophages, leading to M1 macrophage activation. The exosome/miR-19b-3p/SOCS1 axis played a critical pathologic role in tubulointerstitial
inflammation, representing a new therapeutic target for
kidney disease.