Exosomal miR-145-5p promotes apoptosis of renal tubule epithelial cells through the JNK signalling pathway

Abstract

Acute kidney injury (AKI) is the most prevalent extrapulmonary organ failure observed in patients with acute respiratory distress syndrome (ARDS). However, the underlying mechanisms leading to AKI in ARDS remain unclear. Exosomes facilitate intercellular and inter-organ communication via exosomal microRNAs (miRNAs), which potentially contribute to the crosstalk between the lung and kidney in ARDS. Therefore, the purposes of our study were to investigate the involvement of exosomal miRNAs in the development of AKI in ARDS. In current study, Sprague-Dawley rats were induced to develop ARDS via hydrochloric acid aspiration. Nanoparticle tracking analysis, Transmission electron microscopy and western blotting were conducted to analyse the exosomes. Quantitative reverse transcription-polymerase chain reaction and in situ hybridisation showed elevated expression level of miR-145-5p in the circulating exosomes and lung tissue of ARDS rats. Overexpression of miR-145-5p disrupted the proteomic profile of renal proximal tubule epithelial cells, leading to impacts on proteins associated with various biological processes, including apoptosis. We further demonstrate that miR-145-5p overexpression enhanced JNK phosphorylation by directly repressing RBM3 expression and promoted cell apoptosis. In vivo, administration of agomiR-145-5p injection via intravenous route, which subsequently induced renal tubular cell apoptosis. These findings have revealed that miR-145-5p may serve as a novel mediator for the apoptosis of renal cell in the context of ARDS.